Disease Information

General Information of the Disease (ID: DIS00074)

Name	Pancreatic cancer
ICD	ICD-11: 2C10
Resistance Map

Type(s) of Resistant Mechanism of This Disease

ADTT: Aberration of the Drug's Therapeutic Target

DISM: Drug Inactivation by Structure Modification

EADR: Epigenetic Alteration of DNA, RNA or Protein

IDUE: Irregularity in Drug Uptake and Drug Efflux

RTDM: Regulation by the Disease Microenvironment

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s)

10 drug(s) in total

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Cisplatin

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-374b				[1]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	BxPC3-R cells	Pancreas	Homo sapiens (Human)	CVCL_XX78
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Resazurin conversion assay
Mechanism Description	The computational prediction that downregulation of miR-374b likely contributed to the acquisition of resistance to cisplatin in BxPC3-R cells was experimentally tested by transfection of miR-374b into BxPC3-R cells and subsequently measuring cisplatin sensitivity of these cells relative to controls. The results demonstrated that miR-374b transfection significantly reduced drug resistance in BxPC3-R cells to levels approaching those of the parental BxPC3 cells.

Cyclophosphamide

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4)				[2]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cyclophosphamide			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Immunoblotting analysis
Experiment for Drug Resistance	Sulforhodamine B assay
Mechanism Description	CYP3A4 is the most abundant hepatic and intestinal cytochrome P450 enzyme in humans, contributing to the metabolism of various drugs such as benzodiazepines, HIV antivirals, macrolide antibiotics, and statins. CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b) or mouse microRNA-298 (mmu-miR-298), overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a lower sensitivity to cyclophosphamide.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-27b				[2]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cyclophosphamide			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Sulforhodamine B assay
Mechanism Description	CYP3A4 is the most abundant hepatic and intestinal cytochrome P450 enzyme in humans, contributing to the metabolism of various drugs such as benzodiazepines, HIV antivirals, macrolide antibiotics, and statins. CYP3A4 3'UTR-luciferase activity was significantly decreased in human embryonic kidney 293 cells transfected with plasmid that expressed microRNA-27b (miR-27b) or mouse microRNA-298 (mmu-miR-298), overexpression of miR-27b or mmu-miR-298 in PANC1 cells led to a lower sensitivity to cyclophosphamide.

Doxorubicin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-1291				[3]
Sensitive Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell growth		Inhibition	hsa05200
In Vitro Model	H69 cells	Lung	Homo sapiens (Human)	CVCL_8121
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Hsa-miR-1291-directed downregulation of ABCC1 led to a greater intracellular drug accumulation and sensitized the cells to doxorubicin.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance-associated protein 1 (MRP1)				[3]
Sensitive Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell growth		Inhibition	hsa05200
In Vitro Model	H69 cells	Lung	Homo sapiens (Human)	CVCL_8121
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Hsa-miR-1291-directed downregulation of ABCC1 led to a greater intracellular drug accumulation and sensitized the cells to doxorubicin.

Erlotinib

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-124				[4]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Erlotinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-124 overexpression was able to sensitize the response of Capan-1 cells to erlotinib through inhibiting EphA2.
Key Molecule: hsa-mir-497				[5]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Erlotinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	FGF/FGFR signaling pathway		Inhibition	hsa01521
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples. Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer. miR-497 plays a role in modulating the malignant phenotype and chemosensitivity of pancreatic cancer cells by directly inhibition of FGF2 and FGFR1 expression.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Ephrin type-A receptor 2 (EPHA2)				[4]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Erlotinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell viability		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-124 overexpression was able to sensitize the response of Capan-1 cells to erlotinib through inhibiting EphA2.
Key Molecule: Fibroblast growth factor 2 (FGF1)				[5]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Erlotinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	FGF/FGFR signaling pathway		Inhibition	hsa01521
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples. Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer. miR-497 plays a role in modulating the malignant phenotype and chemosensitivity of pancreatic cancer cells by directly inhibition of FGF2 and FGFR1 expression.
Key Molecule: Fibroblast growth factor receptor 1 (FGFR1)				[5]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Erlotinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	FGF/FGFR signaling pathway		Inhibition	hsa01521
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples. Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer. miR-497 plays a role in modulating the malignant phenotype and chemosensitivity of pancreatic cancer cells by directly inhibition of FGF2 and FGFR1 expression.

Everolimus

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1)				[6]
Resistant Disease	Pancreatic neuroendocrine tumor [ICD-11: 2C10.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Everolimus			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K/AKT/mTOR signaling pathway		Activation	hsa04151
	CXCR4-CXCL12-CXCR7 signaling pathway		Activation	hsa04061
In Vitro Model	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	SN12C cells	Kidney	Homo sapiens (Human)	CVCL_1705
Experiment for Molecule Alteration	Western blotting assay
Mechanism Description	When the CXCR4-CXCL12-CXCR7 pathway is activated through CXCL12 in human renal cancer cells were, SN12C and A498, CXCL12 induced the mTOR targets p-P70S6K and p-4EBP1.The combination therapy of mTOR inhibitors with the CXCR4-CXCL12-CXCR7 axis inhibitors in renal cancer tumors could overcome the Everolimus resistance.
Key Molecule: Ribosomal protein S6 kinase beta-1 (RPS6KB1)				[6]
Resistant Disease	Pancreatic neuroendocrine tumor [ICD-11: 2C10.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Everolimus			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K/AKT/mTOR signaling pathway		Activation	hsa04151
	CXCR4-CXCL12-CXCR7 signaling pathway		Activation	hsa04061
In Vitro Model	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	SN12C cells	Kidney	Homo sapiens (Human)	CVCL_1705
Experiment for Molecule Alteration	Western blotting assay
Mechanism Description	When the CXCR4-CXCL12-CXCR7 pathway is activated through CXCL12 in human renal cancer cells were, SN12C and A498, CXCL12 induced the mTOR targets p-P70S6K and p-4EBP1.The combination therapy of mTOR inhibitors with the CXCR4-CXCL12-CXCR7 axis inhibitors in renal cancer tumors could overcome the Everolimus resistance.

Fluorouracil

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: DiGeorge syndrome critical region gene 5 (DGCR5)				[7]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HAPC cells	Pancreas	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	DGCR5 and miR320a regulate each other in a reciprocal manner and that DGCR5 reverses the inhibition of PDCD4 by miR320a, which is involved in the regulation of the PDAC cell phenotype and response to 5-FU. miR320a is involved in 5-FU resistance modulated by DGCR5.
Key Molecule: Growth arrest specific 5 (GAS5)				[8]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Hippo signaling pathway		Inhibition	hsa04390
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	5-FU cells	Colon	Homo sapiens (Human)	CVCL_1846
	PATU8988	Pancreas	Homo sapiens (Human)	CVCL_1847
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	SW1990/GEM cells	Pancreas	Homo sapiens (Human)	CVCL_ZW98
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	GAS5 regualtes Hippo signaling pathway via miR181c-5p to antagonize the development of multidrug resistance in pancreatic cancer cells. GAS5 regulated chemoresistance and Hippo pathway of pancreatic cancer cells via miR181c-5p/Hippo.
Key Molecule: hsa-miR-221-3p				[9]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	293TN cells	Pancreas	Homo sapiens (Human)	CVCL_UL49
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	5-FU and gemcitabine assay; CCK8 assay; Wound healing assay; Transwell chamber invasion assay
Mechanism Description	miRNA-221-3p desensitizes pancreatic cancer cells to 5-fluorouracil by targeting RB1. miR221-3p down-regulated RB1 expression by directly binding to its 3'-UTR and therefore caused increased several aspects of pancreatic cancer pathogenesis, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
Key Molecule: Urothelial cancer associated 1 (UCA1)				[10]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	ERK signaling pathway		Activation	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Wound-healing assay
Mechanism Description	CUDR overexpression inhibits cell apoptosis and promotes drug resistance in PDAC and CUDR overexpression in Panc-1 cells significantly increased phosphorylated (p-) focal adhesion kinase (FAk) and p-AkT levels, whereas the total FAk and AkT were not altered compared with in Panc-1 cells transfected with an empty vector.
Key Molecule: hsa-mir-21				[11]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	PI3K/AKT/mTOR signaling pathway		Regulation	hsa04151
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	293TN cells	Pancreas	Homo sapiens (Human)	CVCL_UL49
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-21 regulates 5-FU drug resistance in pancreatic cancer by reducing the expression of its targets, PTEN and PDCD4. And PTEN and PDCD4, as tumor suppressors, not only can inhibit tumor growth and invasion, but also can downregulate the 5-FU resistance induced by miR-21 in pancreatic cancer cells.
Key Molecule: hsa-mir-181c				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: hsa-miR-1246				[13]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: hsa-mir-320				[14]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	CCK8 assay; Wound Healing assay; Matrigel transmembrane invasion assay
Mechanism Description	miR-320a was up-regulated in 5-FU resistant pancreatic cancer cells and that miR-320a could promote pancreatic cancer cell proliferation, migration and invasion then contributed to the increased 5-FU resistance. Researchers think miR-320a could suppress cell apoptosis by inhibiting PDCD4 and further contribute to drug-resistance, which will be studied in future.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Retinoblastoma-associated protein (RB1)				[9]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	293TN cells	Pancreas	Homo sapiens (Human)	CVCL_UL49
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	5-FU and gemcitabine assay; CCK8 assay; Wound healing assay; Transwell chamber invasion assay
Mechanism Description	miRNA-221-3p desensitizes pancreatic cancer cells to 5-fluorouracil by targeting RB1. miR221-3p down-regulated RB1 expression by directly binding to its 3'-UTR and therefore caused increased several aspects of pancreatic cancer pathogenesis, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
Key Molecule: RAC serine/threonine-protein kinase (AKT)				[10]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	ERK signaling pathway		Activation	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Wound-healing assay
Mechanism Description	CUDR overexpression inhibits cell apoptosis and promotes drug resistance in PDAC and CUDR overexpression in Panc-1 cells significantly increased phosphorylated (p-) focal adhesion kinase (FAk) and p-AkT levels, whereas the total FAk and AkT were not altered compared with in Panc-1 cells transfected with an empty vector.
Key Molecule: Mitogen-activated protein kinase (MAPK)				[10]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	ERK signaling pathway		Activation	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Wound-healing assay
Mechanism Description	CUDR overexpression inhibits cell apoptosis and promotes drug resistance in PDAC and CUDR overexpression in Panc-1 cells significantly increased phosphorylated (p-) focal adhesion kinase (FAk) and p-AkT levels, whereas the total FAk and AkT were not altered compared with in Panc-1 cells transfected with an empty vector.
Key Molecule: Programmed cell death protein 4 (PDCD4)				[11], [14]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	PI3K/AKT/mTOR signaling pathway		Regulation	hsa04151
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	293TN cells	Pancreas	Homo sapiens (Human)	CVCL_UL49
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Wound Healing assay; Matrigel transmembrane invasion assay
Mechanism Description	miR-21 regulates 5-FU drug resistance in pancreatic cancer by reducing the expression of its targets, PTEN and PDCD4. And PTEN and PDCD4, as tumor suppressors, not only can inhibit tumor growth and invasion, but also can downregulate the 5-FU resistance induced by miR-21 in pancreatic cancer cells.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[11]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	PI3K/AKT/mTOR signaling pathway		Regulation	hsa04151
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	293TN cells	Pancreas	Homo sapiens (Human)	CVCL_UL49
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-21 regulates 5-FU drug resistance in pancreatic cancer by reducing the expression of its targets, PTEN and PDCD4. And PTEN and PDCD4, as tumor suppressors, not only can inhibit tumor growth and invasion, but also can downregulate the 5-FU resistance induced by miR-21 in pancreatic cancer cells.
Key Molecule: Serine/threonine-protein kinase LATS2 (LATS2)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: MOB kinase activator 1A (MOB1A)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Serine/threonine-protein kinase 4 (MST1)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Protein salvador homolog 1 (SAV1)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Cyclin-G2 (CCNG2)				[13]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-320				[7]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Inhibition	hsa04670
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	SUDHL-4 cells	Peritoneal effusion	Homo sapiens (Human)	CVCL_0539
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	DGCR5 and miR320a regulate each other in a reciprocal manner and that DGCR5 reverses the inhibition of PDCD4 by miR320a, which is involved in the regulation of the PDAC cell phenotype and response to 5-FU. miR320a is involved in 5-FU resistance modulated by DGCR5. DGCR5 reversed the inhibition of the miR320a target gene PDCD4, which in turn inhibited the proliferation, migration and 5-FU resistance of PDAC cells.
Key Molecule: hsa-miR-181c-5p				[8]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Hippo signaling pathway		Inhibition	hsa04390
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	5-FU cells	Colon	Homo sapiens (Human)	CVCL_1846
	PATU8988	Pancreas	Homo sapiens (Human)	CVCL_1847
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	SW1990/GEM cells	Pancreas	Homo sapiens (Human)	CVCL_ZW98
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Long non-coding RNA GAS5 antagonizes the chemoresistance of pancreatic cancer cells through down-regulation of miR181c-5p. GAS5 negatively regulated miR181c-5p, and miR181c-5p dramatically promoted pancreatic cancer cell chemoresistance through inactivating the Hippo signaling.
Key Molecule: hsa-mir-21				[15]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
	HPAF-II cells	Pancreatic	Homo sapiens (Human)	CVCL_0313
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	SRB (sulforhodamine-B) assay
Mechanism Description	Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro.

Gemcitabine

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Activation induced cytidine deaminase (AICDA)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	The main mechanism for gemcitabine inactivation is through deamination by cytidine deaminase (CDA) to difluorodeoxyuridine (dFdU). Since dFdU is not a substrate for pyrimidine nucleoside phosphorylases, the drug is degraded and excreted out of the cell.
Key Molecule: Deoxycytidine kinase (DCK)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	Once taken up into the cell, gemcitabine is phosphorylated by deoxycytidine kinase (dCK) to produce dFdCMP. In turn, dFdCMP is converted by other pyrimidine kinases to its active diphosphate and triphosphate derivatives, dFdCDP and dFdCTP. Due to the central role of dCK in gemcitabine metabolism, its deficiency is a major contributor to gemcitabine resistance.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-188-3p				[17]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description	Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression.
Key Molecule: P53 regulated carcinoma associated Stat3 activating long intergenic non-protein coding transcript (PRECSIT)				[17]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description	Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression.
Key Molecule: hsa-mir-301				[18]
Resistant Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Colorimetric methylene blue assay; Flow cytometry assay
Mechanism Description	Gemcitabine-resistant Capan-2 and Panc-1 cells exhibited increased miR-301 expression, and miR-301 overepression can enhance apoptosis and inhibit cell invasiveness and exhibit strong gemcitabine resistance.
Key Molecule: Maternally expressed 3 (MEG3)				[19]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	COLO357 cells	Pancreas	Homo sapiens (Human)	CVCL_0221
	T3M4 cells	Pancreas	Homo sapiens (Human)	CVCL_4056
	HTERT-HPNE cells	Pancreas	Homo sapiens (Human)	CVCL_C466
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Boyden chamber assay; Sphere formation assay; Flow cytometric analysis
Mechanism Description	Decreased expression of MEG3 could promote PC cell migration and invasion, as well as chemoresistance by regulating the EMT process and CSC properties.
Key Molecule: HOX transcript antisense RNA (HOTAIR)				[20]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Gemcitabine treatment causes resistance and malignancy of pancreatic cancer stem-like cells via induction of LncRNA HOTAIR.
Key Molecule: Taurine up-regulated 1 (TUG1)				[21]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell viability		Activation	hsa05200
	ERK signaling pathway		Activation	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	PANC-28 cells	Pancreatic	Homo sapiens (Human)	CVCL_3917
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	TUG1 promoted the viability of PDAC cells and enhanced its resistance of gemcitabine and overexpression of TUG1 increased ERk phosphorylation.
Key Molecule: hsa-mir-301				[22]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
Cell Pathway Regulation	Cell viability		Activation	hsa05200
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	HPAF-II cells	Pancreatic	Homo sapiens (Human)	CVCL_0313
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-301a upregulation promoted resistance to gemcitabine under hypoxia through downregulation of TAp63.
Key Molecule: hsa-miR-455-3p				[23]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell viability		Activation	hsa05200
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Down-regulation of microRNA-455-3p Links to Proliferation and Drug Resistance of Pancreatic Cancer Cells via Targeting TAZ.
Key Molecule: hsa-mir-125a				[24]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-125a may promote chemo-resistance to gemcitabine in pancreatic cell lines through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.
Key Molecule: hsa-mir-181c				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: HOXA distal transcript antisense RNA (HOTTIP)				[25]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	HOTTIP/HOXA13 signaling pathway		Activation	hsa05202
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer.Microarray analyses revealed that HOTTIP was one of the most significantly upregulated LncRNAs in PDAC tissues compared with pancreatic tissues.Furthermore, knockdown of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted PDAC cell proliferation, invasion, and chemoresistance, at least partly through regulating HOXA13. As a crucial tumor promoter, HOTTIP promotes cell proliferation, invasion, and chemoresistance by modulating HOXA13. Therefore, the HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for PDAC.
Key Molecule: hsa-miR-1246				[13]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
Key Molecule: hsa-mir-21				[26], [27], [28]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	FasL/Fas signaling pathway		Inhibition	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	LPc006 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc028 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc033 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc067 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc111 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc167 cells	Pancreas	Homo sapiens (Human)	N.A.
	PP437 cells	Pancreas	Homo sapiens (Human)	N.A.
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	WST-8 assay; Fluorescence microscopy
Mechanism Description	miR-21 regulates expression of PTEN and phosphorylation of its downstream kinase Akt and (b) the reduction of phospho-Akt (pAkt) correlated with the enhancement of gemcitabine-induced apoptosis and antitumor activity in vitro and in vivo, suggesting that Akt pathway plays a significant role in mediating drug resistance in PDAC cells.
Key Molecule: hsa-mir-21				[29]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
	BxPc3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Capan cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	HPAF cells	Pancreas	Homo sapiens (Human)	CVCL_B284
	PL-45 cells	Pancreas	Homo sapiens (Human)	CVCL_3567
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAkT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAkT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAkT expressions induced by gemcitabine.
Key Molecule: hsa-mir-365				[30]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-365 directly targets the pro-apoptotic molecules SHC1 and BAX, whose reductions contribute to gemcitabine resistance in pancreatic cancer cells.
Key Molecule: hsa-mir-181				[31]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell viability		Activation	hsa05200
	NF-kappaB signaling pathway		Regulation	hsa04064
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PSN1 cells	Pancreas	Homo sapiens (Human)	CVCL_1644
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-181b enhances the activity of NF-kB by inhibiting CYLD, thus leading to the resistance to gemcitabine.
Key Molecule: hsa-miR-320c				[32]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell viability		Activation	hsa05200
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	PSN1 cells	Pancreas	Homo sapiens (Human)	CVCL_1644
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-320c regulates the resistance of pancreatic cancer cells to gemcitabine through SMARCC1.
Key Molecule: hsa-mir-21				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	miR-21 is probably the most characterized miRNA associated with gemcitabine resistance. Tissue samples of PDA patients treated with gemcitabine indicate that miR-21 expression is directly correlated with chemotherapy resistance. Patients with high miR-21 expression have significantly shorter overall survival; consistently, overexpression of miR-21 in primary PDA cells in vitro, decreases the anti-proliferative effect of gemcitabine. miR-21 promotes gemcitabine resistance by targeting phosphatase and tensin homologue (PTEN) or by overexpression of matrix metalloproteinases (MMP) 2 and 9, and of vascular endothelial growth factor (VEGF), which in-turn induces the PI3K/AKT pathway.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Solute carrier family 29 member 1 (SLC29A1)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	Gemcitabine could be a substrate for several nucleoside transporters (NTs), but its major uptake occurs via the equilibrative and concentrative type NTs (ENTs and CNTs, respectively). ENT1, CNT1 and CNT3 have often been related to gemcitabine transport and resistance in humans. When ENT1 knockout conferred gemcitabine resistance, while its up regulation enhanced its cytotoxic activity. Similarly, retroviral expression of CNT1 renders ovarian cancer cells sensitive to gemcitabine in vitro.
Key Molecule: Solute carrier family 28 member 1 (SLC28A1)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	Gemcitabine could be a substrate for several nucleoside transporters (NTs), but its major uptake occurs via the equilibrative and concentrative type NTs (ENTs and CNTs, respectively). ENT1, CNT1 and CNT3 have often been related to gemcitabine transport and resistance in humans. When ENT1 knockout conferred gemcitabine resistance, while its up regulation enhanced its cytotoxic activity. Similarly, retroviral expression of CNT1 renders ovarian cancer cells sensitive to gemcitabine in vitro.
Key Molecule: Solute carrier family 28 member 3 (SLC28A3)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	Gemcitabine could be a substrate for several nucleoside transporters (NTs), but its major uptake occurs via the equilibrative and concentrative type NTs (ENTs and CNTs, respectively). ENT1, CNT1 and CNT3 have often been related to gemcitabine transport and resistance in humans. When ENT1 knockout conferred gemcitabine resistance, while its up regulation enhanced its cytotoxic activity. Similarly, retroviral expression of CNT1 renders ovarian cancer cells sensitive to gemcitabine in vitro.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: hsa-mir-221				[33]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	miR221/SOCS3 signaling pathway		Regulation	hsa05206
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-221 overexpression can promote proliferation, migration, emt, chemotherapy resistance, and stem cell-like properties in panc-1 cells.
Key Molecule: Transcription factor AP2 gamma (TFAP2C)				[34]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Activation	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
	T3M4 cells	Pancreas	Homo sapiens (Human)	CVCL_4056
In Vivo Model	Nude mouse model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Transwell assay
Mechanism Description	Transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p.
Key Molecule: hsa-miR-10a-5p				[34]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell viability		Activation	hsa05200
	Epithelial mesenchymal transition signaling pathway		Activation	hsa01521
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
	T3M4 cells	Pancreas	Homo sapiens (Human)	CVCL_4056
In Vivo Model	Nude mouse model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Transwell assay
Mechanism Description	Transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p.
Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)				[35]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
In Vitro Model	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	MALAT-1 could increase the proportion of pancreatic CSCs, maintain self-renewing capacity, decrease the chemosensitivity to anticancer drugs, and accelerate tumor angiogenesis in vitro, and promote tumorigenicity of pancreatic cancer cells in vivo. The underlying mechanisms may involve in increased expression of self-renewal related factors Sox2.
Key Molecule: hsa-mir-100				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-10a				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-10b				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-134				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-143				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-146a				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-15				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-205				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-214				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-32				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-34				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-miR-146b-5p				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: hsa-mir-7				[36]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Pancreatic cancers relapse due to small but distinct population of cancer stem cells (CSCs) which are in turn regulated by miRNAs. Those miRNA were either upregulated (e.g. miR-146) or downregulated (e.g. miRNA-205, miRNA-7) in gemcitabine resistant MIA PaCa-2 cancer cells and clinical metastatic pancreatic cancer tissues.
Key Molecule: TIMP metallopeptidase inhibitor 2 (TIMP2)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	The ECM may provide a mechanical barrier, preventing the tumor from further spread. Disintegration of the ECM by MMPs enables cancer cells to dissociate from the tumor and metastasize. Apart from destabilizing the physical barrier, MMPs overexpression also regulates internal cellular cascades. In response to collagen deposition in the ECM, an MMP dependent ERK-1/2 phosphorylation occurs, triggering the transcription factor HMGA2 and gemcitabine resistance.
Key Molecule: Mucin 4, cell surface associated (MUC4)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	Mucin 4 (MUC4) is a membrane-bound O-glycoprotein that is found in the lining of the respiratory tract and GI mucosa, where it enables lubrication and cell-matrix detachment. In PDA, MUC4 expressing cells exhibit greater gemcitabine resistance than do MUC4 negative cells, an effect mediated by interaction with HER2.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Bromodomain-containing protein 4 (BRD4)				[17]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay; Western blot analysis; RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description	Long non-coding RNA LINC00346 promotes pancreatic cancer growth and gemcitabine resistance by sponging miR-188-3p to derepress BRD4 expression.
Key Molecule: Mitogen-activated protein kinase (MAPK)				[21]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell viability		Activation	hsa05200
Cell Pathway Regulation	ERK signaling pathway		Activation	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	PANC-28 cells	Pancreatic	Homo sapiens (Human)	CVCL_3917
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	TUG1 promoted the viability of PDAC cells and enhanced its resistance of gemcitabine and overexpression of TUG1 increased ERk phosphorylation.
Key Molecule: Tumor protein 63 (TP63)				[22]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
Cell Pathway Regulation	Cell viability		Activation	hsa05200
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	HPAF-II cells	Pancreatic	Homo sapiens (Human)	CVCL_0313
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-301a upregulation promoted resistance to gemcitabine under hypoxia through downregulation of TAp63.
Key Molecule: Tafazzin (TAZ)				[23]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell viability		Activation	hsa05200
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Down-regulation of microRNA-455-3p Links to Proliferation and Drug Resistance of Pancreatic Cancer Cells via Targeting TAZ.
Key Molecule: Tumor necrosis factor alpha-induced protein 3 (TNFAIP3)				[24]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-125a may promote chemo-resistance to gemcitabine in pancreatic cell lines through targeting A20, which may provide novel therapeutic targets or molecular biomarkers for cancer therapy and improve tumor diagnosis or predictions of therapeutic responses.
Key Molecule: Serine/threonine-protein kinase LATS2 (LATS2)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: MOB kinase activator 1A (MOB1A)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Serine/threonine-protein kinase 4 (MST1)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Protein salvador homolog 1 (SAV1)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Homeobox protein Hox-A13 (HOXA13)				[25]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	HOTTIP/HOXA13 signaling pathway		Activation	hsa05202
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The long non-coding RNA HOTTIP promotes progression and gemcitabine resistance by regulating HOXA13 in pancreatic cancer.Microarray analyses revealed that HOTTIP was one of the most significantly upregulated LncRNAs in PDAC tissues compared with pancreatic tissues.Furthermore, knockdown of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted PDAC cell proliferation, invasion, and chemoresistance, at least partly through regulating HOXA13. As a crucial tumor promoter, HOTTIP promotes cell proliferation, invasion, and chemoresistance by modulating HOXA13. Therefore, the HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for PDAC.
Key Molecule: Transcription factor SOX-2 (SOX2)				[35]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
In Vitro Model	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	MALAT-1 could increase the proportion of pancreatic CSCs, maintain self-renewing capacity, decrease the chemosensitivity to anticancer drugs, and accelerate tumor angiogenesis in vitro, and promote tumorigenicity of pancreatic cancer cells in vivo. The underlying mechanisms may involve in increased expression of self-renewal related factors Sox2.
Key Molecule: Cyclin-G2 (CCNG2)				[13]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[29]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
	BxPc3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Capan cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	HPAF cells	Pancreas	Homo sapiens (Human)	CVCL_B284
	PL-45 cells	Pancreas	Homo sapiens (Human)	CVCL_3567
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAkT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAkT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAkT expressions induced by gemcitabine.
Key Molecule: Apoptosis regulator BAX (BAX)				[30]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-365 directly targets the pro-apoptotic molecules SHC1 and BAX, whose reductions contribute to gemcitabine resistance in pancreatic cancer cells.
Key Molecule: SHC-transforming protein 1 (SHC1)				[30]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-365 directly targets the pro-apoptotic molecules SHC1 and BAX, whose reductions contribute to gemcitabine resistance in pancreatic cancer cells.
Key Molecule: Ubiquitin carboxyl-terminal hydrolase CYLD (CYLD)				[31]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell viability		Activation	hsa05200
	NF-kappaB signaling pathway		Regulation	hsa04064
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PSN1 cells	Pancreas	Homo sapiens (Human)	CVCL_1644
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-181b enhances the activity of NF-kB by inhibiting CYLD, thus leading to the resistance to gemcitabine.
Key Molecule: SWI/SNF complex subunit SMARCC1 (SMARCC1)				[32]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell viability		Activation	hsa05200
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	PSN1 cells	Pancreas	Homo sapiens (Human)	CVCL_1644
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-320c regulates the resistance of pancreatic cancer cells to gemcitabine through SMARCC1.
Key Molecule: Tumor necrosis factor ligand superfamily member 6 (FASLG)				[28]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	FasL/Fas signaling pathway		Inhibition	hsa04210
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	WST-8 assay
Mechanism Description	Decreased Fas/FasL signaling mediates miR-21-induced chemoresistance in pancreatic cancer, over-expression of miR-21 reduced the endogenous expression of FasL anfd cause resistance to Gemcitabine.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2)				[27]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Upregulation of Bcl-2 expression was detected in cells transfected with miR-21 mimics, accompanied by downregulated Bax expression, less apoptosis, lower caspase-3 activity, decreased chemosensitivity to gemcitabine and increased proliferation.
Key Molecule: RAC serine/threonine-protein kinase (AKT)				[26]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	LPc006 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc028 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc033 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc067 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc111 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc167 cells	Pancreas	Homo sapiens (Human)	N.A.
	PP437 cells	Pancreas	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Fluorescence microscopy
Mechanism Description	miR-21 regulates expression of PTEN and phosphorylation of its downstream kinase Akt and (b) the reduction of phospho-Akt (pAkt) correlated with the enhancement of gemcitabine-induced apoptosis and antitumor activity in vitro and in vivo, suggesting that Akt pathway plays a significant role in mediating drug resistance in PDAC cells.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[26]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	AKT signaling pathway		Activation	hsa04151
	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	LPc006 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc028 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc033 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc067 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc111 cells	Pancreas	Homo sapiens (Human)	N.A.
	LPc167 cells	Pancreas	Homo sapiens (Human)	N.A.
	PP437 cells	Pancreas	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Fluorescence microscopy
Mechanism Description	miR-21 regulates expression of PTEN and phosphorylation of its downstream kinase Akt and (b) the reduction of phospho-Akt (pAkt) correlated with the enhancement of gemcitabine-induced apoptosis and antitumor activity in vitro and in vivo, suggesting that Akt pathway plays a significant role in mediating drug resistance in PDAC cells.
Key Molecule: DNA excision repair protein ERCC-1 (ERCC1)				[16]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	Excision repair cross-complementation 1 (ERCC1) is a DNA repair endonuclease responsible for the incision of DNA cross-link-induced double-strand breaks. ERCC1 can repair gemcitabine-induced strand breaks, and its overexpression is well documented in poor gemcitabine responders.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-663a				[37]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	T3-M4 cells	Pancreas	Homo sapiens (Human)	CVCL_VQ95
Experiment for Molecule Alteration	RT-PCR, qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Colony formation assay; Flow cytometry assay
Mechanism Description	Upregulated miR-663 expression in PDAC cell lines promotes sensitivity to GEM.
Key Molecule: hsa-mir-200b				[18]
Sensitive Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell metastasis		Inhibition	hsa05205
	Cell proliferation		Inhibition	hsa05200
	Chemosensitivity		Activation	hsa05207
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Colorimetric methylene blue assay; Flow cytometry assay
Mechanism Description	Forced expression of miR-200b induces CDH1 expression and promotes gemcitabine sensitivity in Capan-2 and Panc-1 cells.
Key Molecule: hsa-miR-1207-5p				[38]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
In Vivo Model	Engrafted tumor mouse model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Overexpression of the miR-1207 pair improves gemcitabine efficacy in PC cells.
Key Molecule: Pvt1 oncogene (PVT1)				[38]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
In Vivo Model	Engrafted tumor mouse model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	PVT1 inhibition leads to improved efficacy of gemcitabine in PC cells.
Key Molecule: hsa-mir-34				[39]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Slug/PUMA signaling pathway		Regulation	hsa04390
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow Cytometric Analysis, MTT assay; TUNEL staining
Mechanism Description	miR34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA. miR34 enhances sensitization against gemcitabine-mediated apoptosis through the down-regulation of Slug expression, and up-regulation of Slug-dependent PUMA expression.
Key Molecule: hsa-miR-429				[40]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR429 sensitized gemcitabine response in GZ-resistant pancreatic cancer cells via its direct upregulation of PDCD4 expression.
Key Molecule: Pvt1 oncogene (PVT1)				[41]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Muse Cell Cycle Assay; Muse Annexin V and Dead Cell Assay; MTT assay
Mechanism Description	Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2 subunit EZH2, and the LncRNA PVT1 expression.
Key Molecule: hsa-let-7a				[42]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	CXCR4/let-7a/HMGA2 pathway		Regulation	hsa05206
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Transwell assay; Flow cytometric analysis
Mechanism Description	CXCR4/Let-7a axis regulates metastasis and chemoresistance of pancreatic cancer cells through targeting HMGA2. overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of gem inhibited by let-7a.
Key Molecule: CXC chemokine receptor type 4 (CXCR4)				[42]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	CXCR4/let-7a/HMGA2 pathway		Regulation	hsa05206
In Vitro Model	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Transwell assay; Flow cytometric analysis
Mechanism Description	CXCR4/Let-7a axis regulates metastasis and chemoresistance of pancreatic cancer cells through targeting HMGA2. overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of gem inhibited by let-7a.
Key Molecule: hsa-mir-205				[43]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2R cells	Pancreas	Homo sapiens (Human)	CVCL_HA89
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometric analysis
Mechanism Description	miR205 resensitizes GEM-resistant pancreatic cancer cells to GEM and acts as a tumor suppressor miRNA.
Key Molecule: hsa-mir-21				[44]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	Panc02 cells	Pancreas	Homo sapiens (Human)	CVCL_D627
In Vivo Model	Mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Costar Transwell Invasion Assay;
Mechanism Description	Upregulating miR21 in CAFs promoted PDAC desmoplasia and increased its drug resistance to gemcitabine treatment by promoting the activation of cancer-associated fibroblasts (CAFs). miR21 mediates activation of CAFs via down-regulating PDCD4.
Key Molecule: Programmed cell death protein 4 (PDCD4)				[44]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	Panc02 cells	Pancreas	Homo sapiens (Human)	CVCL_D627
In Vivo Model	Mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR; Immunofluorescence (IF) staining
Experiment for Drug Resistance	Costar Transwell Invasion Assay;
Mechanism Description	Upregulating miR21 in CAFs promoted PDAC desmoplasia and increased its drug resistance to gemcitabine treatment by promoting the activation of cancer-associated fibroblasts (CAFs). miR21 mediates activation of CAFs via down-regulating PDCD4.
Key Molecule: hsa-mir-153				[45]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTS assay; Annexin-V/PI Apoptosis assay; TUNEL assay
Mechanism Description	miR153 enhanced gemcitabine sensitivity by targeting Snail in pancreatic cancer.
Key Molecule: hsa-mir-101				[46]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; Annexin V apoptosis assay; Caspase-3 activity assay
Mechanism Description	microRNA-101 silences RNA-Pkcs and sensitizes pancreatic cancer cells to gemcitabine. AntagomiR101 expression causes RNA-Pkcs upregulation and gemcitabine resistance. miR101 expression inhibits Akt activation in PANC-1 cells.
Key Molecule: hsa-mir-210				[47]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
In Vivo Model	Chick egg xenograft model			Gallus gallus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	RealTime-Glo MT Cell Viability Assay; Caspase-3/7 substrate assay; Colony formation assay
Mechanism Description	microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer, miR210 is a direct suppressor of the multidrug efflux transporter ABCC5.
Key Molecule: hsa-mir-145				[48]
Sensitive Disease	Pancreatic adenocarcinoma [ICD-11: 2C10.4]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	RT-PCR; qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Transwell migration assay
Mechanism Description	miRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells, miR145 negatively regulated p70S6k1 expression at the posttranscriptional level in colon cancer.
Key Molecule: hsa-miR-20a-5p				[49]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-20a-5p inhibits protein expression of RRM2 and reverses gemcitabine resistance.
Key Molecule: hsa-mir-30a				[50]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell colony		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	SNAI1/IRS1/AKT signaling pathway		Regulation	hsa04151
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR-30a overexpression suppresses cell proliferation, and sensitizes pancreatic cancer cells to gemcitabine and miR-30a overexpression reduced IRS1 and SNAI1 protein level.
Key Molecule: hsa-miR-373-3p				[51]
Sensitive Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-373-3p enhances the chemosensitivity of gemcitabine through cell cycle pathway by downregulating CCND2 in pancreatic carcinoma cells.
Key Molecule: hsa-mir-29c				[52]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell colony		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-29c targets USP22 and suppresses autophagy-mediated chemoresistance in a xenograft tumor model in vivo.
Key Molecule: hsa-miR-101-3p				[53]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	Long-term treatment of PDA cells with gemcitabine induced pronounced therapy resistance. The RRM1 gene is a major mediator of resistance and its expression is regulated by direct binding of miR-101-3p to two binding sites in the RRM1 3'UTR. The overexpression of miR-101-3p mimics inhibited the expression of RRM1 and partially reversed gemcitabine-resistance.
Key Molecule: hsa-let-7b				[54]
Sensitive Disease	KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	MEK/ERK /PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
In Vitro Model	NCI-H1975 cells	Lung	Homo sapiens (Human)	CVCL_1511
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.
Key Molecule: hsa-mir-21				[55]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Hs-578T cells	Breast	Homo sapiens (Human)	CVCL_0332
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Increased p85alpha expression in PDAC TCs results in decreased PI3k-AkT signaling and increased gemcitabine sensitivity. Expression of p85alpha inversely correlates with miR-21 levels in human PDAC. Overexpression of miR-21 results in decreased levels of p85alpha and increased PI3k-AkT activation.
Key Molecule: hsa-mir-497				[5]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	FGF/FGFR signaling pathway		Inhibition	hsa01521
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples. Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer. miR-497 plays a role in modulating the malignant phenotype and chemosensitivity of pancreatic cancer cells by directly inhibition of FGF2 and FGFR1 expression.
Key Molecule: hsa-mir-211				[56]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
Cell Pathway Regulation	Cell migration		Inhibition	hsa04670
In Vitro Model	Suit2 cells	Pancreas	Homo sapiens (Human)	CVCL_3172
	SUIT2-007 cells	Pancreas	Homo sapiens (Human)	CVCL_B279
	SUIT2-028 cells	Pancreas	Homo sapiens (Human)	CVCL_B282
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Transwell assay
Mechanism Description	The induction of the miR-211 expression in the cells increased the sensitivity to gemcitabine and reduced the expression of its target ribonucleotide reductase subunit 2 (RRM2).
Key Molecule: hsa-mir-29a				[57]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	Wnt/Beta-catenin signaling pathway		Inhibition	hsa04310
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PSN1 cells	Pancreas	Homo sapiens (Human)	CVCL_1644
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Our findings suggest that miR-29a expression correlates significantly with the growth-inhibitory effect of GEM and that activation of the Wnt/beta-catenin signaling pathway mediated the miR-29a-induced resistance to GEM in pancreatic cancer cell lines.
Key Molecule: hsa-mir-181				[58]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vitro Model	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	BCL-2 facilitates cell survival against chemotherapy via the blockage of Bax/Bak-induced apoptosis, miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.
Key Molecule: hsa-miR-142-5p				[59]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
In Vitro Model	SUIT-2 cells	Pancreas	Homo sapiens (Human)	CVCL_3172
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Propidium iodide assay
Mechanism Description	High miR-142-5p expression was significantly associated with longer survival times in the gemcitabine group.
Key Molecule: Pvt1 oncogene (PVT1)				[60]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Genome-wide screening identified PVT1 as a regulator for Gemcitabine sensitivity in human pancreatic cancer cells.
Key Molecule: hsa-mir-21				[15]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
	HPAF-II cells	Pancreatic	Homo sapiens (Human)	CVCL_0313
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	SRB (sulforhodamine-B) assay
Mechanism Description	Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro.
Key Molecule: hsa-mir-21				[61]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	Hs-578T cells	Breast	Homo sapiens (Human)	CVCL_0332
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	SUIT-2 cells	Pancreas	Homo sapiens (Human)	CVCL_3172
	H48N cells	Pancreas	Homo sapiens (Human)	CVCL_D554
	KP-1N cells	Pancreas	Homo sapiens (Human)	CVCL_3002
	KP-2 cells	Pancreas	Homo sapiens (Human)	CVCL_3004
	KP-3 cells	Pancreas	Homo sapiens (Human)	CVCL_3005
	NOR-P1 cells	Pancreas	Homo sapiens (Human)	CVCL_4716
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Propidium iodide assay
Mechanism Description	The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family C5 (ABCC5)				[47]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
In Vivo Model	Chick egg xenograft model			Gallus gallus
Experiment for Molecule Alteration	Dual luciferase assay; qRT-PCR; Immunofluorescence and immunohistochemistry assay
Experiment for Drug Resistance	RealTime-Glo MT Cell Viability Assay; Caspase-3/7 substrate assay; Colony formation assay
Mechanism Description	microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer, miR210 is a direct suppressor of the multidrug efflux transporter ABCC5.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Growth arrest specific 5 (GAS5)				[33]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	miR221/SOCS3 signaling pathway		Regulation	hsa05206
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Overexpression of GAS5 inhibits proliferation, migration, and chemotherapy resistance by suppressing the emt and tumor stem cell-like properties. LncRNA GAS5 functioned as a competing endogenous RNA for miR-221, and it suppressed cell growth, metastasis, and gemcitabine resistance in PC by regulating the miR-221/SOCS3 pathway mediating EMT and tumor stem cell self-renewal.
Key Molecule: Suppressor of cytokine signaling 3 (SOCS3)				[33]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	miR221/SOCS3 signaling pathway		Regulation	hsa05206
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	SOCS3 overexpression reverses miR-221 overexpression-induced proliferation, migration, emt, chemotherapy resistance, and stem cell-like properties in panc-1 cells.
Key Molecule: hsa-mir-3656				[62]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Epithelial mesenchymal transition signaling pathway		Activation	hsa01521
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
	HTERT-HPNE cells	Pancreas	Homo sapiens (Human)	CVCL_C466
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR3656 expression enhances the chemosensitivity of pancreatic cancer to gemcitabine through modulation of the RHOF/EMT axis. miR3656 could target RHOF, a member of the Rho subfamily of small GTPases, and regulate the EMT process, enforced EMT progression via TWIST1 overexpression compromised the chemotherapy-enhancing effects of miR3656. Reduced miR3656 expression levels activated the EMT pathway through upregulation of RHOF, eventually causing drug resistance.
Key Molecule: Rho-related GTP-binding protein RhoF (RHOF)				[62]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Epithelial mesenchymal transition signaling pathway		Activation	hsa01521
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
	HTERT-HPNE cells	Pancreas	Homo sapiens (Human)	CVCL_C466
	PATU8988 cells	Pancreas	Homo sapiens (Human)	CVCL_1846
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	HPAC cells	Pancreas	Homo sapiens (Human)	CVCL_3517
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; Dual luciferase reporter assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR3656 expression enhances the chemosensitivity of pancreatic cancer to gemcitabine through modulation of the RHOF/EMT axis. miR3656 could target RHOF, a member of the Rho subfamily of small GTPases, and regulate the EMT process, enforced EMT progression via TWIST1 overexpression compromised the chemotherapy-enhancing effects of miR3656. Reduced miR3656 expression levels activated the EMT pathway through upregulation of RHOF, eventually causing drug resistance.
Key Molecule: hsa-miR-1243				[63]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
	TGF-beta signaling pathway		Inhibition	hsa04350
In Vitro Model	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	KMP3 cells	Pancreas	Homo sapiens (Human)	CVCL_8491
	KP4-4 cells	Pancreas	Homo sapiens (Human)	CVCL_Y142
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	WST-8 assay; Crystal violet staining assay
Mechanism Description	Overexpression of miR509-5p and miR1243 increased the expression of E-cadherin through the suppression of EMT-related gene expression and that drug sensitivity increased with a combination of each of these miRNAs and gemcitabine. miR1243 directly regulated SMAD2 and SMAD4, which regulate the TGF-beta signaling pathway, resulting in an induction of the MET phenotype. Suppressing SMADs reduced the effect of TGF-beta.
Key Molecule: hsa-miR-509-5p				[63]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
	TGF-beta signaling pathway		Inhibition	hsa04350
In Vitro Model	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	KMP3 cells	Pancreas	Homo sapiens (Human)	CVCL_8491
	KP4-4 cells	Pancreas	Homo sapiens (Human)	CVCL_Y142
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	WST-8 assay; Crystal violet staining assay
Mechanism Description	miR509-5p and miR1243 increase the sensitivity to gemcitabine by inhibiting epithelial-mesenchymal transition in pancreatic cancer miR509-5p induced an MET phenotype by directly regulating VIM and HMGA2.
Key Molecule: Mothers against decapentaplegic homolog 2 (SMAD2)				[63]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
	TGF-beta signaling pathway		Inhibition	hsa04350
In Vitro Model	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	KMP3 cells	Pancreas	Homo sapiens (Human)	CVCL_8491
	KP4-4 cells	Pancreas	Homo sapiens (Human)	CVCL_Y142
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	WST-8 assay; Crystal violet staining assay
Mechanism Description	Overexpression of miR509-5p and miR1243 increased the expression of E-cadherin through the suppression of EMT-related gene expression and that drug sensitivity increased with a combination of each of these miRNAs and gemcitabine. miR1243 directly regulated SMAD2 and SMAD4, which regulate the TGF-beta signaling pathway, resulting in an induction of the MET phenotype. Suppressing SMADs reduced the effect of TGF-beta.
Key Molecule: Mothers against decapentaplegic homolog 4 (SMAD4)				[63]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
	TGF-beta signaling pathway		Inhibition	hsa04350
In Vitro Model	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
	KMP3 cells	Pancreas	Homo sapiens (Human)	CVCL_8491
	KP4-4 cells	Pancreas	Homo sapiens (Human)	CVCL_Y142
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	WST-8 assay; Crystal violet staining assay
Mechanism Description	Overexpression of miR509-5p and miR1243 increased the expression of E-cadherin through the suppression of EMT-related gene expression and that drug sensitivity increased with a combination of each of these miRNAs and gemcitabine. miR1243 directly regulated SMAD2 and SMAD4, which regulate the TGF-beta signaling pathway, resulting in an induction of the MET phenotype. Suppressing SMADs reduced the effect of TGF-beta.
Key Molecule: hsa-mir-155				[64]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	Panc1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	PSN1 cells	Pancreas	Homo sapiens (Human)	CVCL_1644
In Vivo Model	Mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	The increase of miR155 induced two different functions; exosome secretion and chemoresistance ability via facilitating the anti-apoptotic activity.
Key Molecule: Tyrosine-protein kinase Fyn (FYN)				[65]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	PATU8988T cells	Pancreatic	Homo sapiens (Human)	CVCL_1847
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Transwell assay
Mechanism Description	miR-125a-3p is responsible for chemosensitivity in PDAC by inhibiting epithelial-mesenchymal transition via Fyn.
Key Molecule: hsa-miR-125a-3p				[65]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	PATU8988T cells	Pancreatic	Homo sapiens (Human)	CVCL_1847
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Transwell assay
Mechanism Description	miR-125a-3p is responsible for chemosensitivity in PDAC by inhibiting epithelial-mesenchymal transition via Fyn.
Key Molecule: hsa-mir-223				[66]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay; Transwell migration and invasion assay
Mechanism Description	Down-regulation of miR-223 reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells due to down-regulation of its target Fbw7 and subsequent upregulation of Notch-1, which enhances GR cells to gemcitabine sensitivity.
Key Molecule: hsa-let-7b				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	The expression of miR-200b, miR-200c, let-7b, let-7c, let-7d, and let-7e was significantly down-regulated in gemcitabine-resistant cells that showed EMT characteristics such as elongated fibroblastoid morphology, lower expression of epithelial marker E-cadherin, and higher expression of mesenchymal markers such as vimentin and ZEB1.
Key Molecule: hsa-let-7c				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	The expression of miR-200b, miR-200c, let-7b, let-7c, let-7d, and let-7e was significantly down-regulated in gemcitabine-resistant cells that showed EMT characteristics such as elongated fibroblastoid morphology, lower expression of epithelial marker E-cadherin, and higher expression of mesenchymal markers such as vimentin and ZEB1.
Key Molecule: hsa-let-7d				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	The expression of miR-200b, miR-200c, let-7b, let-7c, let-7d, and let-7e was significantly down-regulated in gemcitabine-resistant cells that showed EMT characteristics such as elongated fibroblastoid morphology, lower expression of epithelial marker E-cadherin, and higher expression of mesenchymal markers such as vimentin and ZEB1.
Key Molecule: hsa-let-7e				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	The expression of miR-200b, miR-200c, let-7b, let-7c, let-7d, and let-7e was significantly down-regulated in gemcitabine-resistant cells that showed EMT characteristics such as elongated fibroblastoid morphology, lower expression of epithelial marker E-cadherin, and higher expression of mesenchymal markers such as vimentin and ZEB1.
Key Molecule: hsa-mir-200b				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	Re-expression of miR-200 in gemcitabine-resistant cells showed partial reversal of EMT characteristics as documented by increased expression of E-cadherin and decreased expression of vimentin, ZEB1, and slug. These results suggest that miR-200 family regulates the expression of ZEB1, slug, E-cadherin, and vimentin and that the re-expression of miR-200 could be useful for the reversal of EMT phenotype to mesenchymal-epithelial transition (MET). re-expression of miR-200 by transfection studies or treatment of gemcitabine-resistant cells with either DIM or isoflavone resulted in the down-regulation of ZEB1, slug, and vimentin, which was consistent with morphological reversal of EMT phenotype leading to epithelial morphology.
Key Molecule: hsa-mir-200c				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	Re-expression of miR-200 in gemcitabine-resistant cells showed partial reversal of EMT characteristics as documented by increased expression of E-cadherin and decreased expression of vimentin, ZEB1, and slug. These results suggest that miR-200 family regulates the expression of ZEB1, slug, E-cadherin, and vimentin and that the re-expression of miR-200 could be useful for the reversal of EMT phenotype to mesenchymal-epithelial transition (MET). re-expression of miR-200 by transfection studies or treatment of gemcitabine-resistant cells with either DIM or isoflavone resulted in the down-regulation of ZEB1, slug, and vimentin, which was consistent with morphological reversal of EMT phenotype leading to epithelial morphology.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1)				[67]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	WST-1 assay
Mechanism Description	Re-expression of miR-200 in gemcitabine-resistant cells showed partial reversal of EMT characteristics as documented by increased expression of E-cadherin and decreased expression of vimentin, ZEB1, and slug. These results suggest that miR-200 family regulates the expression of ZEB1, slug, E-cadherin, and vimentin and that the re-expression of miR-200 could be useful for the reversal of EMT phenotype to mesenchymal-epithelial transition (MET). re-expression of miR-200 by transfection studies or treatment of gemcitabine-resistant cells with either DIM or isoflavone resulted in the down-regulation of ZEB1, slug, and vimentin, which was consistent with morphological reversal of EMT phenotype leading to epithelial morphology.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cadherin-1 (CDH1)				[18]
Sensitive Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Colorimetric methylene blue assay; Flow cytometry assay
Mechanism Description	Forced expression of miR-200b induces CDH1 expression and promotes gemcitabine sensitivity in Capan-2 and Panc-1 cells.
Key Molecule: Transforming protein RhoA (RHOA)				[38]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
In Vivo Model	Engrafted tumor mouse model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; qRT-PCR; IHC analyses
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	RhoA inhibition leads to improved efficacy of gemcitabine in PC cells.
Key Molecule: Proto-oncogene tyrosine-protein kinase Src (SRC)				[38]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	Su.86.86 cells	Pancreas	Homo sapiens (Human)	CVCL_3881
In Vivo Model	Engrafted tumor mouse model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; qRT-PCR; IHC analyses
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	SRC inhibition leads to improved efficacy of gemcitabine in PC cells.
Key Molecule: High mobility group protein HMGI-C (HMGA2)				[63], [42]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	CXCR4/let-7a/HMGA2 pathway		Regulation	hsa05206
In Vitro Model	HPDE6-C7 cells	Pancreas	Homo sapiens (Human)	CVCL_0P38
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR; Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay; Transwell assay; Flow cytometric analysis
Mechanism Description	CXCR4/Let-7a axis regulates metastasis and chemoresistance of pancreatic cancer cells through targeting HMGA2. overexpression of HMGA2 restores cell proliferation, metastasis and chemosensitivity of gem inhibited by let-7a.
Key Molecule: Bcl-2-binding component 3 (BBC3)				[39]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Slug/PUMA signaling pathway		Activation	hsa04390
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	RT-PCR; Western blot analysis
Experiment for Drug Resistance	Flow Cytometric Analysis, MTT assay; TUNEL staining
Mechanism Description	miR34 induces Slug-mediated upregulation of PUMA expression. miR34 sensitizes to gemcitabine-mediated apoptosis by PUMA upregulation.
Key Molecule: Zinc finger protein SNAI2 (SNAI2)				[39]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Slug/PUMA signaling pathway		Regulation	hsa04390
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	RT-PCR; Western blot analysis
Experiment for Drug Resistance	Flow Cytometric Analysis, MTT assay; TUNEL staining
Mechanism Description	miR34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting Slug/PUMA. miR34 enhances sensitization against gemcitabine-mediated apoptosis through the down-regulation of Slug expression, and up-regulation of Slug-dependent PUMA expression.
Key Molecule: Programmed cell death protein 4 (PDCD4)				[40]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR429 sensitized gemcitabine response in GZ-resistant pancreatic cancer cells via its direct upregulation of PDCD4 expression.
Key Molecule: Zinc finger protein SNAI1 (SNAI1)				[45]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay; Annexin-V/PI Apoptosis assay; TUNEL assay
Mechanism Description	miR153 enhanced gemcitabine sensitivity by targeting Snail in pancreatic cancer.
Key Molecule: DNA-dependent catalytic protein kinase (PRKDC)				[46]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Annexin V apoptosis assay; Caspase-3 activity assay
Mechanism Description	microRNA-101 silences RNA-Pkcs and sensitizes pancreatic cancer cells to gemcitabine. AntagomiR101 expression causes RNA-Pkcs upregulation and gemcitabine resistance. miR101 expression inhibits Akt activation in PANC-1 cells.
Key Molecule: Ribosomal protein S6 kinase beta-1 (RPS6KB1)				[48]
Sensitive Disease	Pancreatic adenocarcinoma [ICD-11: 2C10.4]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Transwell migration assay
Mechanism Description	miRNA-145 increases therapeutic sensibility to gemcitabine treatment of pancreatic adenocarcinoma cells, miR145 negatively regulated p70S6k1 expression at the posttranscriptional level in colon cancer.
Key Molecule: Ribonucleoside-diphosphate reductase subunit M2 (RRM2)				[49]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-20a-5p inhibits protein expression of RRM2 and reverses gemcitabine resistance.
Key Molecule: Insulin receptor substrate 1 (IRS1)				[50]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell colony		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	SNAI1/IRS1/AKT signaling pathway		Regulation	hsa04151
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR-30a overexpression suppresses cell proliferation, and sensitizes pancreatic cancer cells to gemcitabine and miR-30a overexpression reduced IRS1 and SNAI1 protein level.
Key Molecule: Zinc finger protein SNAI1 (SNAI1)				[50]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell colony		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	SNAI1/IRS1/AKT signaling pathway		Regulation	hsa04151
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR-30a overexpression suppresses cell proliferation, and sensitizes pancreatic cancer cells to gemcitabine and miR-30a overexpression reduced IRS1 and SNAI1 protein level.
Key Molecule: G1/S-specific cyclin-D2 (CCND2)				[51]
Sensitive Disease	Pancreatic carcinoma [ICD-11: 2C10.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-373-3p enhances the chemosensitivity of gemcitabine through cell cycle pathway by downregulating CCND2 in pancreatic carcinoma cells.
Key Molecule: Ubiquitin carboxyl-terminal hydrolase 22 (USP22)				[52]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell colony		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis; RIP assay; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	miR-29c targets USP22 and suppresses autophagy-mediated chemoresistance in a xenograft tumor model in vivo.
Key Molecule: Ribonucleoside-diphosphate reductase large subunit (RRM1)				[53]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	Long-term treatment of PDA cells with gemcitabine induced pronounced therapy resistance. The RRM1 gene is a major mediator of resistance and its expression is regulated by direct binding of miR-101-3p to two binding sites in the RRM1 3'UTR. The overexpression of miR-101-3p mimics inhibited the expression of RRM1 and partially reversed gemcitabine-resistance.
Key Molecule: Ribonucleoside-diphosphate reductase subunit M2 (RRM2)				[54]
Sensitive Disease	KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	MEK/ERK /PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
In Vitro Model	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.
Key Molecule: Tubulin beta-3 chain (TUBB3)				[54]
Sensitive Disease	KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	MEK/ERK /PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.
Key Molecule: PI3-kinase regulatory subunit alpha (PIK3R1)				[55]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Hs-578T cells	Breast	Homo sapiens (Human)	CVCL_0332
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	Increased p85alpha expression in PDAC TCs results in decreased PI3k-AkT signaling and increased gemcitabine sensitivity. Expression of p85alpha inversely correlates with miR-21 levels in human PDAC. Overexpression of miR-21 results in decreased levels of p85alpha and increased PI3k-AkT activation.
Key Molecule: F-box/WD repeat-containing protein 7 (FBXW7)				[66]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vitro Model	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Transwell migration and invasion assay
Mechanism Description	Down-regulation of miR-223 reverses epithelial-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells due to down-regulation of its target Fbw7 and subsequent upregulation of Notch-1, which enhances GR cells to gemcitabine sensitivity.
Key Molecule: Fibroblast growth factor 2 (FGF1)				[5]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	FGF/FGFR signaling pathway		Inhibition	hsa01521
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples. Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer. miR-497 plays a role in modulating the malignant phenotype and chemosensitivity of pancreatic cancer cells by directly inhibition of FGF2 and FGFR1 expression.
Key Molecule: Fibroblast growth factor receptor 1 (FGFR1)				[5]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
	FGF/FGFR signaling pathway		Inhibition	hsa01521
In Vitro Model	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples. Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer. miR-497 plays a role in modulating the malignant phenotype and chemosensitivity of pancreatic cancer cells by directly inhibition of FGF2 and FGFR1 expression.
Key Molecule: Ribonucleoside-diphosphate reductase subunit M2 (RRM2)				[56]
Sensitive Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
Cell Pathway Regulation	Cell migration		Inhibition	hsa04670
In Vitro Model	Suit2 cells	Pancreas	Homo sapiens (Human)	CVCL_3172
	SUIT2-007 cells	Pancreas	Homo sapiens (Human)	CVCL_B279
	SUIT2-028 cells	Pancreas	Homo sapiens (Human)	CVCL_B282
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Transwell assay
Mechanism Description	The induction of the miR-211 expression in the cells increased the sensitivity to gemcitabine and reduced the expression of its target ribonucleotide reductase subunit 2 (RRM2).
Key Molecule: Apoptosis regulator Bcl-2 (BCL2)				[58]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gemcitabine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	SW1990 cells	Pancreas	Homo sapiens (Human)	CVCL_1723
In Vitro Model	CFPAC1 cells	Pancreas	Homo sapiens (Human)	CVCL_1119
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	BCL-2 facilitates cell survival against chemotherapy via the blockage of Bax/Bak-induced apoptosis, miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.

Paclitaxel

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-181c				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase LATS2 (LATS2)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: MOB kinase activator 1A (MOB1A)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Serine/threonine-protein kinase 4 (MST1)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.
Key Molecule: Protein salvador homolog 1 (SAV1)				[12]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Hippo signaling pathway		Regulation	hsa04392
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and (+) expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-let-7b				[54]
Sensitive Disease	KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	MEK/ERK /PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	A549 cells	Lung	Homo sapiens (Human)	CVCL_0023
	NCI-H1975 cells	Lung	Homo sapiens (Human)	CVCL_1511
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Ribonucleoside-diphosphate reductase subunit M2 (RRM2)				[54]
Sensitive Disease	KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	MEK/ERK /PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.
Key Molecule: Tubulin beta-3 chain (TUBB3)				[54]
Sensitive Disease	KRAS mutant pancreatic ductal adenocarcinoma [ICD-11: 2C10.5]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	MEK/ERK /PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Let-7b repletion selectively sensitized kRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type kRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEk/ERk and PI3k/AkT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in kRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of beta-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of kRAS mutant tumors.

Penfluridol

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Autophagy-related protein LC3 B (MAP1LC3B)				[68]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Penfluridol			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	A549/Taxol cells	Lung	Homo sapiens (Human)	CVCL_W218
	SW403 cells	Colon	Homo sapiens (Human)	CVCL_0545
In Vivo Model	Athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	SRB assay
Mechanism Description	One of the hallmarks of autophagy is the accumulation of LC3B and its localization in vesicular structures. We observed that penfluridol treatment enhanced the expression of LC3B and hence induced autophagy in pancreatic cancer cells.

Trametinib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF)				[69]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Missense mutation		p.K601E (c.1801A>G)	Molecule Info
Resistant Drug	Trametinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
	A375 cells	Skin	Homo sapiens (Human)	CVCL_0132
	NIH-3T3 cells	Embryo	Mus musculus (Mouse)	CVCL_0594
	NT-3 cells	Lymph node	Homo sapiens (Human)	CVCL_VG81
Experiment for Drug Resistance	BioRad TC20 automated cell counter assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF)				[70]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Complex-indel		p.V487_P492delinsA (c.1460_1474del15)	Molecule Info
Sensitive Drug	Trametinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	A375 cells	Skin	Homo sapiens (Human)	CVCL_0132
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	NIH 3T3 cells	Colon	Homo sapiens (Human)	CVCL_0594
	HEK 293 cells	Kidney	Homo sapiens (Human)	CVCL_0045
	OV-90 cells	Ascites	Homo sapiens (Human)	CVCL_3768
	H2405 cells	Lung	Homo sapiens (Human)	CVCL_1551
In Vivo Model	NIH nude rat xenograft model			Rattus norvegicus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF)				[71]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	IF-deletion		p.N486_P490delNVTAP (c.1457_1471del15)	Molecule Info
Sensitive Drug	Trametinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Blood sample			.

Clinical Trial Drug(s)

4 drug(s) in total

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TRAIL

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: HOX transcript antisense RNA (HOTAIR)				[72]
Resistant Disease	Pancreatic cancer [ICD-11: 2C10.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	TRAIL			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Suit2 cells	Pancreas	Homo sapiens (Human)	CVCL_3172
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometric analysis
Mechanism Description	The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand.

MK-2206

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: GTPase KRas (KRAS)			[73]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Missense mutation	p.G12D (c.35G>A)	Molecule Info
Sensitive Drug	MK-2206		Drug Info
Experimental Note	Identified from the Human Clinical Data
Mechanism Description	The missense mutation p.G12D (c.35G>A) in gene KRAS cause the sensitivity of MK-2206 by unusual activation of pro-survival pathway

LY3009120

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)			Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF)				[70]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Complex-indel		p.V487_P492delinsA (c.1460_1474del15)	Molecule Info
Sensitive Drug	LY3009120			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	HCT116 cells	Colon	Homo sapiens (Human)	CVCL_0291
	A375 cells	Skin	Homo sapiens (Human)	CVCL_0132
	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	NIH 3T3 cells	Colon	Homo sapiens (Human)	CVCL_0594
	HEK 293 cells	Kidney	Homo sapiens (Human)	CVCL_0045
	OV-90 cells	Ascites	Homo sapiens (Human)	CVCL_3768
	H2405 cells	Lung	Homo sapiens (Human)	CVCL_1551
In Vivo Model	NIH nude rat xenograft model			Rattus norvegicus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay

OSI-027

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-663a				[37]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	OSI-027			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	T3-M4 cells	Pancreas	Homo sapiens (Human)	CVCL_VQ95
Experiment for Molecule Alteration	RT-PCR, qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Colony formation assay; Flow cytometry assay
Mechanism Description	Gemcitabine enhances OSI-027 cytotoxicity by upregulation of miR-663a in pancreatic ductal adenocarcinoma cells.

Preclinical Drug(s)

1 drug(s) in total

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Spliceostatin A

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)			Click to Show/Hide
Key Molecule: Splicing factor 3B subunit 1 (SF3B1)				[74]
Sensitive Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Missense mutation		p.K700E (c.2098A>G)	Molecule Info
Sensitive Drug	Spliceostatin A			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	HEC1A cells	Uterus	Homo sapiens (Human)	CVCL_0293
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	Capan-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0026
	Pancreatic Panc 0504 cells	Pancreas	Homo sapiens (Human)	CVCL_1637
	MFE296 cells	Endometrium	Homo sapiens (Human)	CVCL_1406
	HEC59 cells	Endometrium	Homo sapiens (Human)	CVCL_2930
	ESS-1 cells	Endometrium	Homo sapiens (Human)	CVCL_1205
	DSMZ cells	N.A.	.	N.A.
	ESS-1 cells	Endometrium	Homo sapiens (Human)	CVCL_1205
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CellTiter-Glo assay

Investigative Drug(s)

2 drug(s) in total

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Cisplatinum

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: MACC1 antisense RNA 1 (MACC1-AS1)				[75]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Up-regulation		Expression	Molecule Info
Resistant Drug	Cisplatinum			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PAX8/NOTCH1 signaling pathway		Activation	hsa04330
In Vitro Model	BxPC-3 cells	Pancreas	Homo sapiens (Human)	CVCL_0186
	MIA PaCa-2 cells	Pancreas	Homo sapiens (Human)	CVCL_0428
	PANC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0480
	Capan-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0237
	AsPC-1 cells	Pancreas	Homo sapiens (Human)	CVCL_0152
	KP-2 cells	Pancreas	Homo sapiens (Human)	CVCL_3004
In Vivo Model	Male BALB/c nude mice xenograft model			Mus musculus
Experiment for Molecule Alteration	Microarray assay; qRT-PCR; Western bloting analysis; Luciferase assay; RIP experiments assay; RNA pull down assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long non-coding RNA MACC1-AS1 promoted pancreatic carcinoma progression through activation of PAX8/NOTCH1 signaling pathway.

Gemcitabine/Trametinib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: GTPase KRas (KRAS)			[76]
Resistant Disease	Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Molecule Alteration	Other	p.G12_G13 (c.34_39)	Molecule Info
Resistant Drug	Gemcitabine/Trametinib		Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Pancreas		.
Experiment for Drug Resistance	Plasma analysis

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Prof. Feng ZHU (zhufeng@zju.edu.cn)