Drug Information

Drug (ID: DG00154) and It's Reported Resistant Information

Name	Epirubicin
Synonyms	Ellence; Epiadriamycin; Epidoxorubicin; Epirubicina; Epirubicine; Epirubicinum; Pidorubicin; Pidorubicina; Pidorubicine; Pidorubicinum; Ridorubicin; Epirubicina [Spanish]; Epirubicine [French]; Epirubicinum [Latin]; Pharmorubicin Pfs; IMI 28; WP 697; Ebewe (TN); Ellence (TN); Epi-DX; Epirubicin (INN); Epirubicin (TN); Epirubicin [INN:BAN]; Epirubicina [INN-Spanish]; Epirubicine [INN-French]; Epirubicinum [INN-Latin]; Farmorubicin (TN); Pharmorubicin (TN); Pidorubicina [INN-Spanish]; Pidorubicine [INN-French]; Pidorubicinum [INN-Latin]; (1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-(methyloxy)-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-arabino-hexopyranoside; (1S,3S)-3,5,12-trihydroxy-3-(hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-arabino-hexopyranoside; (7S,9R)-7-[(2S,4S,5R,6S)-4-Amino-5-hydroxy-6-methyl-oxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione; (7S,9S)-7-[(2R,4S,5R,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione; 10-((3-amino-2,3,6-trideoxy-beta-L-arabino-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-(8S-cis)-5,12-naphthacenedione; 4'-Epi-DXR; 4'-Epiadriamycin; 4'-epi-DX; 4'-epi-Doxorubicin; 4'-epidoxorubicin; 4-Epidoxorubicin Click to Show/Hide
Indication	In total 1 Indication(s) Solid tumour/cancer [ICD-11: 2A00-2F9Z] Approved [1]
Structure
Drug Resistance Disease(s)	Disease(s) with Clinically Reported Resistance for This Drug (3 diseases) Bladder cancer [ICD-11: 2C94] [2] Breast cancer [ICD-11: 2C60] [3] Lung cancer [ICD-11: 2C25] [4] Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases) Bladder cancer [ICD-11: 2C94] [6] Breast cancer [ICD-11: 2C60] [7] Sarcoma [ICD-11: 2C35] [8]
Target	DNA topoisomerase II (TOP2)	TOP2A_HUMAN ; TOP2B_HUMAN	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	C27H29NO11
IsoSMILES	C[C@H]1[C@@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O
InChI	1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22-,27-/m0/s1
InChIKey	AOJJSUZBOXZQNB-VTZDEGQISA-N
PubChem CID	41867
ChEBI ID	CHEBI:47898
TTD Drug ID	D0C9XJ
VARIDT ID	DR00170
INTEDE ID	DR0591
DrugBank ID	DB00445

Type(s) of Resistant Mechanism of This Drug

DISM: Drug Inactivation by Structure Modification

EADR: Epigenetic Alteration of DNA, RNA or Protein

IDUE: Irregularity in Drug Uptake and Drug Efflux

MRAP: Metabolic Reprogramming via Altered Pathways

RTDM: Regulation by the Disease Microenvironment

UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

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Lung cancer [ICD-11: 2C25]

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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: Inositol polyphosphate-4-phosphatase type I A (INPP4A)				[4]
Resistant Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Lung cancer [ICD-11: 2C25]
The Specified Disease	Non-small cell lung cancer
The Studied Tissue	Lung tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.08E-06 Fold-change: -1.11E-01 Z-score: -5.07E+00
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell viability		Activation	hsa05200
	JAKT2/STAT3 signaling pathway		Activation	hsa04030
In Vitro Model	H1299 cells	Lung	Homo sapiens (Human)	CVCL_0060
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	Overexpression of miR-4443 promotes the resistance of non-small cell lung cancer cells to epirubicin by downregulating INPP4A and regulating the activation of JAk2/STAT3 pathway.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-4443				[4]
Resistant Disease	Non-small cell lung cancer [ICD-11: 2C25.Y]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell viability		Activation	hsa05200
	JAKT2/STAT3 signaling pathway		Activation	hsa04030
In Vitro Model	H1299 cells	Lung	Homo sapiens (Human)	CVCL_0060
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	Overexpression of miR-4443 promotes the resistance of non-small cell lung cancer cells to epirubicin by downregulating INPP4A and regulating the activation of JAk2/STAT3 pathway.

Bladder cancer [ICD-11: 2C94]

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Metabolic Reprogramming via Altered Pathways (MRAP)			Click to Show/Hide
Key Molecule: Urothelial cancer associated 1 (UCA1)				[2]
Metabolic Type	Lipid metabolism
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Bladder cancer [ICD-11: 2C94]
The Specified Disease	Bladder urothelial carcinoma
The Studied Tissue	Bladder
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 3.99E-08 Fold-change: 1.93E+00 Z-score: 6.03E+00
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	Nude mice, 5637 bladder cancer cells were transduced with sh-NC lentivirus; nude mice, 5637 bladder cancer cells were transduced with sh-UCA1 lentivirus			Mice
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARalpha mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARalpha and downstream p-AKT/p-GSK-3beta/beta-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRalpha to the lncRNA UCA1 promoter.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[2]
Metabolic Type	Lipid metabolism
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vivo Model	Patients with high expression of lncRNA UCA1			Homo Sapiens
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Cell prognosis assay
Mechanism Description	Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARalpha mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARalpha and downstream p-AKT/p-GSK-3beta/beta-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRalpha to the lncRNA UCA1 promoter.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[2]
Metabolic Type	Lipid metabolism
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	UMUC-2 cells	Bladder	Homo sapiens (Human)	CVCL_8155
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Cell viability assay
Mechanism Description	Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPARalpha mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPARalpha and downstream p-AKT/p-GSK-3beta/beta-catenin signaling. Furthermore, mixed free fatty acids upregulated lncRNA UCA1 expression by promoting recruitment of the transcription factor RXRalpha to the lncRNA UCA1 promoter.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[2]
Metabolic Type	Lipid metabolism
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vivo Model	BALB/c nude mice			Mice
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Tumor volume assay
Mechanism Description	Our findings demonstrate that lncRNA UCA1 positively regulates the expression of CD36 and FATP, which are known to stimulate fatty acid uptake.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[2]
Metabolic Type	Lipid metabolism
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	DSMZ cells	N.A.	N.A.	N.A.
	UMUC-2 cells	Bladder	Homo sapiens (Human)	CVCL_8155
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Apoptosis rate assay
Mechanism Description	Our findings demonstrate that lncRNA UCA1 positively regulates the expression of CD36 and FATP, which are known to stimulate fatty acid uptake.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-34b-3p				[19]
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	Notch/PkC/Ca++ signaling pathway		Inhibition	hsa04330
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	EJ cells	Bladder	Homo sapiens (Human)	CVCL_UI82
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.
Key Molecule: hsa-miR-22-3p				[6]
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	T24 cells	Bladder	Homo sapiens (Human)	CVCL_0554
	UM-UC-3 cells	Bladder	Homo sapiens (Human)	CVCL_1783
	H-bc cells	Bladder	Homo sapiens (Human)	CVCL_BT00
	HTB-1 cells	Bladder	Homo sapiens (Human)	CVCL_0359
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: G1/S-specific cyclin-D2 (CCND2)				[19]
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	Notch/PkC/Ca++ signaling pathway		Inhibition	hsa04330
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	EJ cells	Bladder	Homo sapiens (Human)	CVCL_UI82
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	miR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.
Key Molecule: P2Y purinoceptor 1 (P2RY1)				[19]
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	Notch/PkC/Ca++ signaling pathway		Inhibition	hsa04330
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	EJ cells	Bladder	Homo sapiens (Human)	CVCL_UI82
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	miR-34b-3p Represses the Multidrug-Chemoresistance of Bladder Cancer Cells by Regulating the CCND2 and P2RY1 Genes.
Key Molecule: Neuroepithelial cell-transforming gene 1 protein (NET1)				[6]
Resistant Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	T24 cells	Bladder	Homo sapiens (Human)	CVCL_0554
	UM-UC-3 cells	Bladder	Homo sapiens (Human)	CVCL_1783
	H-bc cells	Bladder	Homo sapiens (Human)	CVCL_BT00
	HTB-1 cells	Bladder	Homo sapiens (Human)	CVCL_0359
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR 22 3p enhances multi chemoresistance by targeting NET1 in bladder cancer cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Lymphoid enhancer-binding factor 1 (LEF1)				[9]
Sensitive Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Bladder cancer [ICD-11: 2C94]
The Specified Disease	Bladder cancer
The Studied Tissue	Bladder tissue
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 1.80E-01 Fold-change: -1.76E-02 Z-score: -1.40E+00
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell colony		Inhibition	hsa05200
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
	Wnt/Beta-catenin signaling pathway		Regulation	N.A.
In Vitro Model	BIU87 cells	Bladder	Homo sapiens (Human)	CVCL_6881
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis.
Key Molecule: Transcription factor 7 (TCF7)				[9]
Sensitive Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell colony		Inhibition	hsa05200
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell viability		Inhibition	hsa05200
	Wnt/Beta-catenin signaling pathway		Regulation	N.A.
In Vitro Model	BIU87 cells	Bladder	Homo sapiens (Human)	CVCL_6881
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis.
Key Molecule: Presenilin-1 (PSEN1)				[20]
Sensitive Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	DNA damage response signaling pathway		Activation	hsa04218
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	H-bc cells	Bladder	Homo sapiens (Human)	CVCL_BT00
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[21]
Sensitive Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	lncRNA UCA1/miR-30a-3p/PPARalpha signaling pathway		Regulation	N.A.
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	In this study, we demonstrated that lncRNA UCA1 inhibits epirubicin-induced cell apoptosis by supporting abnormal lipid metabolism in bladder cancer cells. Mechanistically, lncRNA UCA1 promotes lipid accumulation in vitro and in vivo by upregulating PPAR mRNA and protein expression, which is mediated by miR-30a-3p. Knockdown of lncRNA UCA1 increased epirubicin-induced apoptosis via miR-30a-3p/PPAR and downstream p-AKT/p-GSK-3beta/beta-catenin signaling.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-34				[9]
Sensitive Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell colony		Inhibition	hsa05200
	Cell invasion		Inhibition	hsa05200
	Cell viability		Inhibition	hsa05200
	Wnt/Beta-catenin signaling pathway		Regulation	N.A.
In Vitro Model	BIU87 cells	Bladder	Homo sapiens (Human)	CVCL_6881
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis.
Key Molecule: hsa-miR-193a-3p				[20]
Sensitive Disease	Bladder cancer [ICD-11: 2C94.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	DNA damage response signaling pathway		Activation	hsa04218
In Vitro Model	5637 cells	Bladder	Homo sapiens (Human)	CVCL_0126
	H-bc cells	Bladder	Homo sapiens (Human)	CVCL_BT00
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.

Multiple myeloma [ICD-11: 2A83]

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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: Aurora kinase A (AURKA)				[10]
Sensitive Disease	Multiple myeloma [ICD-11: 2A83.0]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Differential expression of the molecule in resistant disease
Classification of Disease	Multiple myeloma [ICD-11: 2A83]
The Specified Disease	Myeloma
The Studied Tissue	Peripheral blood
The Expression Level of Disease Section Compare with the Healthy Individual Tissue	p-value: 5.27E-01 Fold-change: -1.02E-01 Z-score: -6.42E-01
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	NCI-H929 cells	Bone marrow	Homo sapiens (Human)	CVCL_1600
	U266 cells	Bone marrow	Homo sapiens (Human)	CVCL_0566
	MM1S cells	Peripheral blood	Homo sapiens (Human)	CVCL_8792
	OPM-2 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1625
	RPMI-8226 cells	Peripheral blood	Homo sapiens (Human)	CVCL_0014
	KMS11 cells	Peripheral blood	Homo sapiens (Human)	CVCL_2989
In Vivo Model	Mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Ectopic expression of miR137 strongly reduced the expression of AURkA and p-ATM/Chk2 in MM cells, and increased the expression of p53, and p21, overexpression of miR137 could reduce drug resistance and overcome chromosomal instability of the MM cells via affecting the apoptosis and RNA damage pathways.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-137				[10]
Sensitive Disease	Multiple myeloma [ICD-11: 2A83.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	NCI-H929 cells	Bone marrow	Homo sapiens (Human)	CVCL_1600
	U266 cells	Bone marrow	Homo sapiens (Human)	CVCL_0566
	MM1S cells	Peripheral blood	Homo sapiens (Human)	CVCL_8792
	OPM-2 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1625
	RPMI-8226 cells	Peripheral blood	Homo sapiens (Human)	CVCL_0014
	KMS11 cells	Peripheral blood	Homo sapiens (Human)	CVCL_2989
In Vivo Model	Mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Ectopic expression of miR137 strongly reduced the expression of AURkA and p-ATM/Chk2 in MM cells, and increased the expression of p53, and p21, overexpression of miR137 could reduce drug resistance and overcome chromosomal instability of the MM cells via affecting the apoptosis and RNA damage pathways.

Liver cancer [ICD-11: 2C12]

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Cytochrome P450 family 1 subfamily B member1 (CYP1B1)				[11]
Sensitive Disease	Liver cancer [ICD-11: 2C12.6]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	N.A.
In Vitro Model	HepG2 cells	Liver	Homo sapiens (Human)	CVCL_0027
	SNU182 cells	Liver	Homo sapiens (Human)	CVCL_0090
	SNU-739 cells	Liver	Homo sapiens (Human)	CVCL_5088
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-27b				[11]
Sensitive Disease	Liver cancer [ICD-11: 2C12.6]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	N.A.
In Vitro Model	HepG2 cells	Liver	Homo sapiens (Human)	CVCL_0027
	SNU182 cells	Liver	Homo sapiens (Human)	CVCL_0090
	SNU-739 cells	Liver	Homo sapiens (Human)	CVCL_5088
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cyclin-G1 (CCNG1)				[11]
Sensitive Disease	Liver cancer [ICD-11: 2C12.6]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	N.A.
In Vitro Model	HepG2 cells	Liver	Homo sapiens (Human)	CVCL_0027
	SNU182 cells	Liver	Homo sapiens (Human)	CVCL_0090
	SNU-739 cells	Liver	Homo sapiens (Human)	CVCL_5088
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.

Sarcoma [ICD-11: 2C35]

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2)				[8]
Resistant Disease	Sarcoma [ICD-11: 2C35.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW-872 cells	Skin	Homo sapiens (Human)	CVCL_1730
	SW-1353 cells	Brain	Homo sapiens (Human)	CVCL_0543
	TE-671 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1756
	SW-684 cells	Skin	Homo sapiens (Human)	CVCL_1726
	SW-982 cells	Testicular	Homo sapiens (Human)	CVCL_1734
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1)				[8]
Resistant Disease	Sarcoma [ICD-11: 2C35.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW-872 cells	Skin	Homo sapiens (Human)	CVCL_1730
	SW-1353 cells	Brain	Homo sapiens (Human)	CVCL_0543
	TE-671 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1756
	SW-684 cells	Skin	Homo sapiens (Human)	CVCL_1726
	SW-982 cells	Testicular	Homo sapiens (Human)	CVCL_1734
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.
Key Molecule: Myc proto-oncogene protein (MYC)				[8]
Resistant Disease	Sarcoma [ICD-11: 2C35.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW-872 cells	Skin	Homo sapiens (Human)	CVCL_1730
	SW-1353 cells	Brain	Homo sapiens (Human)	CVCL_0543
	TE-671 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1756
	SW-684 cells	Skin	Homo sapiens (Human)	CVCL_1726
	SW-982 cells	Testicular	Homo sapiens (Human)	CVCL_1734
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.
Key Molecule: Transcription factor SOX-2 (SOX2)				[8]
Resistant Disease	Sarcoma [ICD-11: 2C35.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW-872 cells	Skin	Homo sapiens (Human)	CVCL_1730
	SW-1353 cells	Brain	Homo sapiens (Human)	CVCL_0543
	TE-671 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1756
	SW-684 cells	Skin	Homo sapiens (Human)	CVCL_1726
	SW-982 cells	Testicular	Homo sapiens (Human)	CVCL_1734
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.
Key Molecule: Catenin beta interacting protein 1 (CTNNBIP1)				[8]
Resistant Disease	Sarcoma [ICD-11: 2C35.0]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW-872 cells	Skin	Homo sapiens (Human)	CVCL_1730
	SW-1353 cells	Brain	Homo sapiens (Human)	CVCL_0543
	TE-671 cells	Peripheral blood	Homo sapiens (Human)	CVCL_1756
	SW-684 cells	Skin	Homo sapiens (Human)	CVCL_1726
	SW-982 cells	Testicular	Homo sapiens (Human)	CVCL_1734
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, beta-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

Breast cancer [ICD-11: 2C60]

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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-129-5p				[1]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 toxicity assay
Mechanism Description	NONHSAT101069 was upregulated in BC tissues and promoted epirubicin resistance, migration and invasion of BC cells via regulation of NONHSAT101069/miR-129-5p/Twist1 axis, highlighting its potential as an oncogene and a therapeutic biomarker for BC.
Key Molecule: Long non-protein coding RNA (NONHSAT101069)				[1]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	SUM1315 cells	Breast	Homo sapiens (Human)	CVCL_5589
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR,Northern blot
Experiment for Drug Resistance	CCK8 toxicity assay
Mechanism Description	Twist1 is a target protein of miR-129-5p and positively regulates by NONHSAT101069 in BC cells. and it stimulates epirubicin resistance, migration, invasion, and EMT progression of BC cells.
Key Molecule: H19, imprinted maternally expressed transcript (H19)				[12]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cullin4A/MDR1 signaling pathway		Regulation	N.A.
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
Experiment for Molecule Alteration	Quantitative real-time RT-PCR
Experiment for Drug Resistance	CellTiter AQueous One Solution Cell Proliferation Assay
Mechanism Description	LncRNA H19 is a major mediator of doxorubicin chemoresistance in breast cancer cells through a cullin4A-MDR1 pathway. H19 overexpression was contributed to cancer cell resistance to anthracyclines and paclitaxel as knockdown of H19 LncRNA by a specific H19 shRNA in Dox-resistant cells significantly improved the cell sensitivity to anthracyclines and paclitaxel.
Key Molecule: Bcl-2-interacting killer (BIK)				[7]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	ZR75-1 cells	Breast	Homo sapiens (Human)	CVCL_0588
	MCF-7R cells	Breast	Homo sapiens (Human)	CVCL_Y493
	ZR-75-1R cells	Breast	Homo sapiens (Human)	CVCL_0588
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Annexin V apoptosis assay; Fow cytometry analysis
Mechanism Description	LncRNA H19 attenuated cell apoptosis in response to PTX treatment by inhibiting transcription of pro-apoptotic genes BIk and NOXA.
Key Molecule: Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)				[7]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	ZR75-1 cells	Breast	Homo sapiens (Human)	CVCL_0588
	MCF-7R cells	Breast	Homo sapiens (Human)	CVCL_Y493
	ZR-75-1R cells	Breast	Homo sapiens (Human)	CVCL_0588
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Annexin V apoptosis assay; Fow cytometry analysis
Mechanism Description	LncRNA H19 attenuated cell apoptosis in response to PTX treatment by inhibiting transcription of pro-apoptotic genes BIk and NOXA.
Key Molecule: hsa-let-7a				[13]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	SkBR3 cells	Breast	Homo sapiens (Human)	CVCL_0033
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Lower let-7a expression was associated with epirubicin resistance in primary breast tumors. Moreover, upregulation of let-7a expression sensitized resistant breast tumor cell lines to epirubicin by enhancing cellular apoptosis in vitro. Collectively, these findings indicate that lower expression of let-7a miRNA can induce chemoresistance in breast cancer by enhancing cellular apoptosis and suggest that let-7a may be used as a therapeutic target to modulate epirubicin-based chemotherapy resistance.
Key Molecule: hsa-mir-204				[14]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Low miR-024 expression was enhancing chemotherapeutic resistance of breast cancer patients.
Key Molecule: hsa-mir-125b				[3]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	p53 signaling pathway		Inhibition	hsa04115
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	T47D cells	Breast	Homo sapiens (Human)	CVCL_0553
	BT20 cells	Breast	Homo sapiens (Human)	CVCL_0178
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Trypan blue dye exclusion assay
Mechanism Description	E2F3, and in some settings E2F1, induce apoptosis through p53-dependent or -independent pathways, Overexpression of miR-125b in MCF-7 cells significantly down-regulated E2F3 protein level, overexpression of miR-125b caused a marked inhibition of anticancer drug activity and increased resistance in breast cancer cells in vitro.
Metabolic Reprogramming via Altered Pathways (MRAP)			Click to Show/Hide
Key Molecule: 6-Phosphogluconate dehydrogenase (6PGD)				[15]
Metabolic Type	Glucose metabolism
Resistant Disease	Breast adenocarcinoma [ICD-11: 2C60.1]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Adrenergic signaling in cardiomyocytes		Activation	hsa04261
In Vitro Model	BT-549 cells	Breast	Homo sapiens (Human)	CVCL_1092
	MDA-MB-23 cells1	Breast	Homo sapiens (Human)	CVCL_0062
Experiment for Molecule Alteration	qRT-PCR; Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	In summary, this study investigated the important role of 6PGD in promoting TNBC progression and attenuating chemotherapy response efficacy of chemotherapy-resistant cells. Inhibition of 6PGD and epirubicin exerted synergistic effects on resistant cells, effectively increasing the sensitivity of resistant cells to chemotherapeutic agents through metabolic remodeling. Therefore, 6PGD might be a potential and important metabolic target in clinical applications such as reversing chemotherapy resistance in TNBC and tumor therapies.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Cyclin-G2 (CCNG2)				[16]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
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	CCK8 assay
Mechanism Description	Exosomal microRNA miR1246 promotes cell proliferation, invasion and drug resistance by suppressing the expression level of CCNG2 in Breast Cancer.
Key Molecule: hsa-miR-1246				[16]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
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	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Exosomal microRNA miR1246 promotes cell proliferation, invasion and drug resistance by suppressing the expression level of CCNG2 in Breast Cancer.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Twist-related protein 1 (TWST1)				[1]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	SUM1315 cells	Breast	Homo sapiens (Human)	CVCL_5589
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR; luciferase reporter assay; Western blot analysis
Experiment for Drug Resistance	CCK8 toxicity assay
Mechanism Description	Twist1 is a target protein of miR-129-5p and positively regulates by NONHSAT101069 in BC cells. and it stimulates epirubicin resistance, migration, invasion, and EMT progression of BC cells.
Key Molecule: Transcription factor E2F3 (E2F3)				[3]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	p53 signaling pathway		Inhibition	hsa04115
In Vitro Model	MCF-7 cells	Breast	Homo sapiens (Human)	CVCL_0031
	MDA-MB-231 cells	Breast	Homo sapiens (Human)	CVCL_0062
	T47D cells	Breast	Homo sapiens (Human)	CVCL_0553
	BT20 cells	Breast	Homo sapiens (Human)	CVCL_0178
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Trypan blue dye exclusion assay
Mechanism Description	E2F3, and in some settings E2F1, induce apoptosis through p53-dependent or -independent pathways, Overexpression of miR-125b in MCF-7 cells significantly down-regulated E2F3 protein level, overexpression of miR-125b caused a marked inhibition of anticancer drug activity and increased resistance in breast cancer cells in vitro.
Key Molecule: Fanconi anemia group D2 protein (FANCD2)				[17]
Resistant Disease	Breast cancer [ICD-11: 2C60.3]			Disease Info
Molecule Alteration	Missense mutation		p.G56V	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	ATF2/ATF3/ATF4 signaling pathway		Inhibition	hsa04915
In Vitro Model	Plasma	Blood	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Circulating-free DNA assay; Whole exome sequencing assay
Mechanism Description	Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance.
Key Molecule: Hyaluronan mediated motility receptor (HMMR)				[18]
Resistant Disease	Breast adenocarcinoma [ICD-11: 2C60.1]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	RHAMM signaling pathway		Regulation	N.A.
In Vitro Model	231-EPIR cells	Breast	Homo sapiens (Human)	N.A.
	M-EPIR cells	Breast	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	We demonstrated that RHAMM immensely contributes to breast cancer chemoresistance by several mechanisms: promoting proliferation and migration, enrichment of breast cancer stemness, and induction of EMT. Also, we found that RHAMM served as a potent prognostic factor in breast cancer patients, especially in those who received chemotherapy.

Prostate cancer [ICD-11: 2C82]

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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: Lactate dehydrogenase A (LDHA)			[5]
Resistant Disease	Prostate cancer [ICD-11: 2C82.0]		Disease Info
Molecule Alteration	Expression	Up-regulation	Molecule Info
Mechanism Description	7928 genes were identified as genes related to tumor progression and metastasis. Of these, 7 genes were found to be associated with PCa prognosis. The scRNA-seq and TCGA data showed that the expression of LDHA was higher in tumors and associated with poor prognosis of PCa. In addition, upregulation of LDHA in PCa cells induces osteoclast differentiation. Additionally, high LDHA expression was associated with resistance to Epirubicin, Elliptinium acetate, and doxorubicin. Cellular experiments demonstrated that LDHA knockdown inhibited doxorubicin resistance in PCa cells.

Kidney cancer [ICD-11: 2C90]

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Cytochrome P450 family 1 subfamily B member1 (CYP1B1)				[11]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	N.A.
In Vitro Model	769-P cells	Kidney	Homo sapiens (Human)	CVCL_1050
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-27b				[11]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]			Disease Info
Molecule Alteration	Expression		Up-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	N.A.
In Vitro Model	769-P cells	Kidney	Homo sapiens (Human)	CVCL_1050
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cyclin-G1 (CCNG1)				[11]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]			Disease Info
Molecule Alteration	Expression		Down-regulation	Molecule Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	N.A.
In Vitro Model	769-P cells	Kidney	Homo sapiens (Human)	CVCL_1050
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CellTiter-Glo luminescent cell viability assay
Mechanism Description	miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.

References

Ref 1	Long non-coding RNA NONHSAT101069 promotes epirubicin resistance, migration, and invasion of breast cancer cells through NONHSAT101069/miR-129-5p/Twist1 axis. Oncogene. 2019 Nov;38(47):7216-7233. doi: 10.1038/s41388-019-0904-5. Epub 2019 Aug 23.
Ref 2	Long noncoding RNA UCA1 inhibits epirubicin-induced apoptosis by activating PPARalpha-mediated lipid metabolism. Exp Cell Res. 2024 Oct 1;442(2):114271.
Ref 3	Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012;7(4):e34210. doi: 10.1371/journal.pone.0034210. Epub 2012 Apr 16.
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Prof. Feng ZHU (zhufeng@zju.edu.cn)