Disease Information

General Information of the Disease (ID: DIS00097)

Name	Kidney cancer
ICD	ICD-11: 2C90
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)

19 drug(s) in total

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Cabozantinib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Pro-angiogenic factors				[1]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cabozantinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	VeroE6/TMPRSS2 cells	Kidney	Chlorocebus sabaeus (Green monkey) (Cercopithecus sabaeus)	CVCL_YQ49
	HUVEC cells	Endothelium	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Secreted protein measurements assay
Experiment for Drug Resistance	Flow cytometry
Mechanism Description	We show that circulating immune cells from patients with ccRCC induce cabozantinib resistance via increased secretion of a set of pro-angiogenic factors.

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: SET and MYND domain containing 2 (SMYD2)				[2]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
In Vivo Model	Balb/c athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	SMYD2 is a histone methyltransferase.The estimated IC50 values of cisplatin, doxorubicin, or 5-FU (but not docetaxel) for AZ505-treated RCC cells were significantly lower than those for the control cells, indicating that the SMYD2 inhibition enhanced the drug sensitivity in renal cancer cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-148a				[3]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Caspase signaling pathway		Activation	hsa04210
In Vitro Model	Caki cells	Kidney	Homo sapiens (Human)	CVCL_0234
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay; PI/Annexin staining assay
Mechanism Description	miR148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells, transfection with the miR148a mimics resulted in the activation of caspase pathway.
Key Molecule: hsa-mir-27b				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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: Ras-related protein Rab-14 (RAB14)				[3]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Caspase signaling pathway		Activation	hsa04210
In Vitro Model	Caki cells	Kidney	Homo sapiens (Human)	CVCL_0234
Experiment for Molecule Alteration	RT-PCR; Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay; PI/Annexin staining assay
Mechanism Description	miR148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells, transfection with the miR148a mimics resulted in the activation of caspase pathway.
Key Molecule: Cyclin-G1 (CCNG1)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.

Daunorubicin

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[5]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Daunorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Flp-In-293/Mock cells	Kidney	Homo sapiens (Human)	CVCL_U421
	Flp-In-293/ABCB1 cells	Kidney	Homo sapiens (Human)	CVCL_U421
Experiment for Molecule Alteration	ATPase assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Docetaxel

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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: SET and MYND domain containing 2 (SMYD2)				[2]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Docetaxel			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
In Vivo Model	Balb/c athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	SMYD2 is a histone methyltransferase.The estimated IC50 values of cisplatin, doxorubicin, or 5-FU (but not docetaxel) for AZ505-treated RCC cells were significantly lower than those for the control cells, indicating that the SMYD2 inhibition enhanced the drug sensitivity in renal cancer cells.

Dovitinib lactate

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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-21				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Dovitinib lactate			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Dovitinib lactate			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Dovitinib lactate			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Metalloproteinase inhibitor 3 (TIMP3)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Dovitinib lactate			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.

Doxorubicin

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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-451				[7]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	GRC-1 cells	Kidney	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Annexin V-FITC Apoptosis Detection assay; MTT assay
Mechanism Description	microRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2 gene.
Key Molecule: SET and MYND domain containing 2 (SMYD2)				[2]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Doxorubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
In Vivo Model	Balb/c athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	SMYD2 is a histone methyltransferase.The estimated IC50 values of cisplatin, doxorubicin, or 5-FU (but not docetaxel) for AZ505-treated RCC cells were significantly lower than those for the control cells, indicating that the SMYD2 inhibition enhanced the drug sensitivity in renal cancer cells.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cyclic AMP-dependent transcription factor ATF-2 (ATF2)				[7]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	GRC-1 cells	Kidney	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Annexin V-FITC Apoptosis Detection assay; MTT assay
Mechanism Description	microRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2 gene.

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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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-708				[8]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
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 apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	TRAIL-mediated signaling pathway		Regulation	hsa04210
In Vitro Model	Caki cells	Kidney	Homo sapiens (Human)	CVCL_0234
Experiment for Molecule Alteration	RT-PCR; RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	C-FLIPL expression was upregulated while miR-708 expression was downregulated in RCC tissues compared to normal tissues. miR-708 functioned as a pro-apoptotic miRNA via specific downregulation of c-FLIPL expression but did not have any effect on the expression of c-FLIPs, which can also increase the drug sensitivity of renal cancer cells.
Key Molecule: hsa-mir-27b				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[5]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Flp-In-293/Mock cells	Kidney	Homo sapiens (Human)	CVCL_U421
	Flp-In-293/ABCB1 cells	Kidney	Homo sapiens (Human)	CVCL_U421
Experiment for Molecule Alteration	ATPase assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: CASP8 and FADD-like apoptosis regulator (CFLAR)				[8]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
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 apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	TRAIL-mediated signaling pathway		Regulation	hsa04210
In Vitro Model	Caki cells	Kidney	Homo sapiens (Human)	CVCL_0234
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	C-FLIPL expression was upregulated while miR-708 expression was downregulated in RCC tissues compared to normal tissues. miR-708 functioned as a pro-apoptotic miRNA via specific downregulation of c-FLIPL expression but did not have any effect on the expression of c-FLIPs, which can also increase the drug sensitivity of renal cancer cells.
Key Molecule: Cyclin-G1 (CCNG1)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.

Epirubicin

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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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Epirubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Epirubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Epirubicin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.

Etoposide

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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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.

Everolimus

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: hsa-mir-92a				[9]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Everolimus			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Caki-1 cells	Kidney	Homo sapiens (Human)	CVCL_0234
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	NC886 also promotes renal cancer cell drug-resistance to Sunitinib or Everolimus by promoting EMT through Rock2 phosphorylation-mediated nuclear translocation of beta-catenin.

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: SET and MYND domain containing 2 (SMYD2)				[2]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Fluorouracil			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
In Vivo Model	Balb/c athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	SMYD2 is a histone methyltransferase.The estimated IC50 values of cisplatin, doxorubicin, or 5-FU (but not docetaxel) for AZ505-treated RCC cells were significantly lower than those for the control cells, indicating that the SMYD2 inhibition enhanced the drug sensitivity in renal cancer cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-21				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: hsa-mir-381				[10]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Fluorouracil			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
	WEE1/Cdc2 signaling pathway		Activation	hsa04110
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
In Vitro Model	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-381 increases sensitivity of 786-O cells to 5-FU by inhibitory WEE1 and increase of Cdc2activity.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Metalloproteinase inhibitor 3 (TIMP3)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Wee1-like protein kinase (WEE1)				[10]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Fluorouracil			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
	WEE1/Cdc2 signaling pathway		Activation	hsa04110
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
In Vitro Model	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-381 increases sensitivity of 786-O cells to 5-FU by inhibitory WEE1 and increase of Cdc2activity.

Gefitinib

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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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gefitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Gefitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Gefitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.

Imatinib

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)			Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT)				[11]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Dimerisation		Up-regulation	Molecule Info
Resistant Drug	Imatinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK 293 cells	Kidney	Homo sapiens (Human)	CVCL_0045
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Flow cytometry
Mechanism Description	These results demonstrated that the c-kit mutation drove auto-dimerisation, and promoted receptor phosphorylation, and ligand-independent receptor signalling pathway. Therefore, dimerisation is the common step in both the activation processes of KIT prior to phosphorylation and therefore, blocking receptor dimerisation may be more effective than blocking the phosphorylated receptor.

Oxaliplatin

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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-21				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Oxaliplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Oxaliplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Oxaliplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Metalloproteinase inhibitor 3 (TIMP3)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Oxaliplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.

Paclitaxel

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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-21				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.
Key Molecule: Metalloproteinase inhibitor 3 (TIMP3)				[6]
Sensitive Disease	Renal carcinoma [ICD-11: 2C90.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	RCC10 cells	Kidney	Homo sapiens (Human)	CVCL_6265
	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Celltiter96 Aqueous Non Radioactive Cell Proliferation Assay
Mechanism Description	Tumor suppressor genes like PTEN, PDCD4 and TIMP3, are target genes of miR21. PTEN is a potent inhibitor of PI3k/Akt pathway, as well as a direct target of miR21.

Sorafenib

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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: Interleukin-6 (IL6)				[12]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sorafenib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell cytotoxicity		Activation	hsa04650
Cell Pathway Regulation	Tumorigenesis		Inhibition	hsa05200
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
	OSRC-2 cells	Kidney	Homo sapiens (Human)	CVCL_1626
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma. LncRNA-SRLR directly binds to NF-kB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance.
Key Molecule: LncRNA sorafenib resistance in renal cell carcinoma associated (LNCSRLR)				[12]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sorafenib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Sorafenib tolerance		Activation	hsa00983
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
	OSRC-2 cells	Kidney	Homo sapiens (Human)	CVCL_1626
Experiment for Molecule Alteration	Microarray assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma. LncRNA-SRLR directly binds to NF-kB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Signal transducer activator transcription 3 (STAT3)				[12]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sorafenib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Sorafenib tolerance		Activation	hsa00983
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
	OSRC-2 cells	Kidney	Homo sapiens (Human)	CVCL_1626
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Long noncoding RNA-SRLR elicits intrinsic sorafenib resistance via evoking IL-6/STAT3 axis in renal cell carcinoma. LncRNA-SRLR directly binds to NF-kB and promotes IL-6 transcription, leading to the activation of STAT3 and the development of sorafenib tolerance.

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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Sorafenib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Sorafenib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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)				[4]
Sensitive Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Sorafenib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR27b/CCNG1/p53 signaling pathway		Regulation	hsa05206
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.

Sunitinib

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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-130b				[13]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	Caki-1 cells	Kidney	Homo sapiens (Human)	CVCL_0234
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-130b promoted cell growth and was associated with sunitinib resistance through regulating PTEN expression.
Key Molecule: hsa-miR-144-3p				[14]
Resistant Disease	Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell metastasis		Activation	hsa05205
	Cell proliferation		Activation	hsa05200
	Chemoresistance		Activation	hsa05207
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR144-3p promotes cell proliferation, metastasis, sunitinib resistance in clear cell renal cell carcinoma by downregulating ARID1A. and the downregulation of ARIDIA could promote the function of mir144-3p in cell proliferation, metastasis and chemoresistance.
Key Molecule: Long non-protein coding RNA SARCC(SARCC)				[15]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell adhesion		Inhibition	hsa04514
	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	Caki-1 cells	Kidney	Homo sapiens (Human)	CVCL_0234
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	769-P cells	Kidney	Homo sapiens (Human)	CVCL_1050
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
	Hk2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	OSRC-2 cells	Kidney	Homo sapiens (Human)	CVCL_1626
	SW839 cells	Kidney	Homo sapiens (Human)	CVCL_3604
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay; Wound-healing assay; Transwell assay
Mechanism Description	LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR143-3p expression, thus inhibition of its downstream signals including AkT, MMP-13, k-RAS and P-ERk. Increased the expression of LncRNA-SARCC decreased RCC cells resistance to Sunitinib.
Key Molecule: hsa-miR-143-3p				[15]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cancer progression		Inhibition	hsa05200
In Vitro Model	Caki-1 cells	Kidney	Homo sapiens (Human)	CVCL_0234
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	769-P cells	Kidney	Homo sapiens (Human)	CVCL_1050
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
	Hk2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
	OSRC-2 cells	Kidney	Homo sapiens (Human)	CVCL_1626
	SW839 cells	Kidney	Homo sapiens (Human)	CVCL_3604
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR; RNA pull-down assay; ChIP assay
Experiment for Drug Resistance	MTT assay; Wound-healing assay; Transwell assay
Mechanism Description	LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR143-3p expression, thus inhibition of its downstream signals including AkT, MMP-13, k-RAS and P-ERk. Increased the expression of LncRNA-SARCC decreased RCC cells resistance to Sunitinib.
Key Molecule: LncRNA regulator of Akt signaling associated with HCC and RCC (LNCARSR)				[16]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	ERK signaling pathway		Regulation	hsa04210
	STAT3/AKT signaling pathway		Regulation	hsa04550
In Vitro Model	771R-luc cells	Kidney	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	qPCR; Northern blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Here we identified an LncRNA, named lncARSR (LncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response.
Key Molecule: hsa-mir-133a				[17]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
In Vitro Model	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line.
Key Molecule: hsa-miR-484				[17]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
In Vitro Model	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line.
Key Molecule: hsa-miR-628-5p				[17]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
In Vitro Model	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line.
Key Molecule: hsa-mir-942				[17]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	High miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance.
Key Molecule: SET and MYND domain containing 2 (SMYD2)				[2]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	HEK293T cells	Kidney	Homo sapiens (Human)	CVCL_0063
	HK-2 cells	Kidney	Homo sapiens (Human)	CVCL_0302
In Vivo Model	Balb/c athymic nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	SMYD2 is a histone methyltransferase.The estimated IC50 values of cisplatin, doxorubicin, or 5-FU (but not docetaxel) for AZ505-treated RCC cells were significantly lower than those for the control cells, indicating that the SMYD2 inhibition enhanced the drug sensitivity in renal cancer cells.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: hsa-mir-92a				[9]
Resistant Disease	Kidney cancer [ICD-11: 2C90.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Caki-1 cells	Kidney	Homo sapiens (Human)	CVCL_0234
	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
	ACHN cells	Pleural effusion	Homo sapiens (Human)	CVCL_1067
	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	NC886 also promotes renal cancer cell drug-resistance to Sunitinib or Everolimus by promoting EMT through Rock2 phosphorylation-mediated nuclear translocation of beta-catenin.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Phosphatase and tensin homolog (PTEN)				[13]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	Caki-1 cells	Kidney	Homo sapiens (Human)	CVCL_0234
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-130b promoted cell growth and was associated with sunitinib resistance through regulating PTEN expression.
Key Molecule: AT-rich interactive domain-containing protein 1A (ARID1A)				[14]
Resistant Disease	Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell metastasis		Activation	hsa05205
	Cell proliferation		Activation	hsa05200
	Chemoresistance		Activation	hsa05207
In Vitro Model	786-O cells	Kidney	Homo sapiens (Human)	CVCL_1051
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Luciferase reporter assay; Western blot analysis; Immunohistochemical staining assay
Experiment for Drug Resistance	MTS assay
Mechanism Description	miR144-3p promotes cell proliferation, metastasis, sunitinib resistance in clear cell renal cell carcinoma by downregulating ARID1A. and the downregulation of ARIDIA could promote the function of mir144-3p in cell proliferation, metastasis and chemoresistance.
Key Molecule: Tyrosine-protein kinase UFO (AXL)				[16]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	ERK signaling pathway		Regulation	hsa04210
	STAT3/AKT signaling pathway		Regulation	hsa04550
In Vitro Model	771R-luc cells	Kidney	Homo sapiens (Human)	N.A.
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Here we identified an LncRNA, named lncARSR (LncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response.
Key Molecule: Hepatocyte growth factor receptor (MET)				[16]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	ERK signaling pathway		Regulation	hsa04210
	STAT3/AKT signaling pathway		Regulation	hsa04550
In Vitro Model	771R-luc cells	Kidney	Homo sapiens (Human)	N.A.
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Here we identified an LncRNA, named lncARSR (LncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response.
Key Molecule: Platelet-derived growth factor receptor alpha (PDGFRA)				[17]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	High miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance.
Key Molecule: Platelet-derived growth factor receptor beta (PDGFRB)				[17]
Resistant Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Caki-2 cells	Kidney	Homo sapiens (Human)	CVCL_0235
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	High miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-141				[18]
Sensitive Disease	Clear cell renal cell carcinoma [ICD-11: 2C90.Y]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Sunitinib			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell viability		Inhibition	hsa05200
In Vitro Model	RCC4 cells	Kidney	Homo sapiens (Human)	CVCL_0498
	UMRC-2 cells	Kidney	Homo sapiens (Human)	CVCL_2739
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Compared to good responders, microRNA-141 was significantly down-regulated in tumors of poor responders to sunitinib. This seemed spatially linked toepithelial-to-mesenchymaltransitioninvivo. microRNA-141 down-regulation driven epithelial-to-mesenchymal transition in clear cell renal cell carcinoma was linked to anunfavorable response to sunitinib therapy.

Topotecan

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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-21				[19]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Topotecan			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	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	XTT assay
Mechanism Description	Inhibition of miR-21 rescues PDCD4 and PTEN protein levels and improves chemosensitivity and therapeutic response.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4)				[19]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Topotecan			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	A498 cells	Kidney	Homo sapiens (Human)	CVCL_1056
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	XTT assay
Mechanism Description	Inhibition of miR-21 rescues PDCD4 and PTEN protein levels and improves chemosensitivity and therapeutic response.

Vinblastine

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[5]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Vinblastine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Flp-In-293/Mock cells	Kidney	Homo sapiens (Human)	CVCL_U421
	Flp-In-293/ABCB1 cells	Kidney	Homo sapiens (Human)	CVCL_U421
Experiment for Molecule Alteration	ATPase assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Vincristine

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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[5]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Vincristine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Flp-In-293/Mock cells	Kidney	Homo sapiens (Human)	CVCL_U421
	Flp-In-293/ABCB1 cells	Kidney	Homo sapiens (Human)	CVCL_U421
Experiment for Molecule Alteration	ATPase assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Through calcein assays, we found that epimagnolin A inhibited the ABCB1-mediated export of calcein. This result suggests that epimagnolin A behaved as inhibitor or substrate for ABCB1. In ATPase assays, epimagnolin A stimulated ABCB1-dependent ATPase activity. This result indicates that epimagnolin A was recognised as a substrate by ABCB1, since ABCB1 utilises energy derived from ATP hydrolysis for substrate transport. Furthermore, in MTT assays we found that the cytotoxicity of daunorubicin, doxorubicin, vinblastine, and vincristine was enhanced by epimagnolin A in a manner comparable to verapamil, a typical substrate for ABCB1.

Investigative Drug(s)

1 drug(s) in total

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MET inhibitors

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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: Hepatocyte growth factor receptor (MET)			[20]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Copy number gain	.	Molecule Info
Sensitive Drug	MET inhibitors		Drug Info
Experimental Note	Identified from the Human Clinical Data
Key Molecule: Hepatocyte growth factor receptor (MET)			[20]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Missense mutation	p.H1094R (c.3281A>G)	Molecule Info
Sensitive Drug	MET inhibitors		Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Renal cell carcinoma tissue		.
Mechanism Description	The missense mutation p.H1094R (c.3281A>G) in gene MET cause the sensitivity of MET inhibitors by aberration of the drug's therapeutic target
Key Molecule: Hepatocyte growth factor receptor (MET)			[21]
Sensitive Disease	Renal cell carcinoma [ICD-11: 2C90.0]
Molecule Alteration	Missense mutation	p.M1268T (c.3803T>C)	Molecule Info
Sensitive Drug	MET inhibitors		Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Human renal cell carcinoma tissue		.
Mechanism Description	The missense mutation p.M1268T (c.3803T>C) in gene MET cause the sensitivity of MET inhibitors by aberration of the drug's therapeutic target

References

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Ref 3	miR-148a increases the sensitivity to cisplatin by targeting Rab14 in renal cancer cells. Int J Oncol. 2017 Mar;50(3):984-992. doi: 10.3892/ijo.2017.3851. Epub 2017 Jan 17.
Ref 4	miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression. Cell Res. 2015 Apr;25(4):477-95. doi: 10.1038/cr.2015.23. Epub 2015 Feb 20.
Ref 5	Epimagnolin A, a tetrahydrofurofuranoid lignan from Magnolia fargesii, reverses ABCB1-mediated drug resistance .Phytomedicine. 2018 Dec 1;51:112-119. doi: 10.1016/j.phymed.2018.06.030. Epub 2018 Jun 20. 10.1016/j.phymed.2018.06.030
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Ref 7	MicroRNA-451 regulates chemoresistance in renal cell carcinoma by targeting ATF-2 gene. Exp Biol Med (Maywood). 2017 Jun;242(12):1299-1305. doi: 10.1177/1535370217701625. Epub 2017 Apr 21.
Ref 8	Inhibition of c-FLIPL expression by miRNA-708 increases the sensitivity of renal cancer cells to anti-cancer drugs. Oncotarget. 2016 May 31;7(22):31832-46. doi: 10.18632/oncotarget.7149.
Ref 9	Nc886 promotes renal cancer cell drug-resistance by enhancing EMT through Rock2 phosphorylation-mediated Beta-catenin nuclear translocation .Cell Cycle. 2022 Feb;21(4):340-351. doi: 10.1080/15384101.2021.2020431. Epub 2022 Jan 2. 10.1080/15384101.2021.2020431
Ref 10	miR-381, a novel intrinsic WEE1 inhibitor, sensitizes renal cancer cells to 5-FU by up-regulation of Cdc2 activities in 786-O. J Chemother. 2013 Aug;25(4):229-38. doi: 10.1179/1973947813Y.0000000092. Epub 2013 May 7.
Ref 11	Management of metastatic gastrointestinal stromal tumour in the Glivec era: a practical case-based approach .Intern Med J. 2006 Jun;36(6):367-77. doi: 10.1111/j.1445-5994.2006.01077.x. 10.1111/j.1445-5994.2006.01077.x
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Prof. Feng ZHU (zhufeng@zju.edu.cn)