Disease Information

General Information of the Disease (ID: DIS00094)

Name	Cervical cancer
ICD	ICD-11: 2C77
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)

16 drug(s) in total

Click to Show/Hide the Full List of Drugs

Baicalein

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Long non-protein coding RNA (BDLNR)				[1]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Baicalein			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Inhibition	hsa04151
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Glo cell viability assays
Mechanism Description	Baicalein inhibits cervical cancer progression via downregulating long noncoding RNA BDLNR and its downstream PI3 k/Akt pathway. BDLNR physically bound to YBX1, recruited YBX1 to PIk3CA promoter, activated PIk3CA expression and PI3 k/Akt pathway.

Bleomycin

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-126				[2]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Bleomycin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Upregulation of miR-126 inhibited cervical cancer cell proliferation and enhanced the sensitivity to BLM. Thus, miR-126 may represent a novel approach to cervical cancer treatment.

Bortezomib

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-101				[3]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Bortezomib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-101 functions as an endogenous proteasome inhibitor by targeting POMP. Targeting POMP is essential for cell growth suppression by miR-101. High miR-101 levels have good outcomes for ERalpha-positive breast cancer patients. Targeting POMP inhibits tumor progression and overcomes resistance to bortezomib.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Proteasome maturation protein (POMP)				[3]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Bortezomib			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-101 functions as an endogenous proteasome inhibitor by targeting POMP. Targeting POMP is essential for cell growth suppression by miR-101. High miR-101 levels have good outcomes for ERalpha-positive breast cancer patients. Targeting POMP inhibits tumor progression and overcomes resistance to bortezomib.

Cisplatin

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Growth arrest specific 5 (GAS5)				[4]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	STAT3 signaling pathway		Activation	hsa04550
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description	Down-regulation of LncRNA GAS5 strengthen cisplatin-induced apoptosis in cervical cancer by regulating STAT3 signaling via miR-21.
Key Molecule: hsa-mir-21				[4]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	STAT3 signaling pathway		Activation	hsa04550
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description	Down-regulation of LncRNA GAS5 strengthen cisplatin-induced apoptosis in cervical cancer by regulating STAT3 signaling via miR-21.
Key Molecule: Cancer susceptibility 2 (CASC2)				[5]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
	H8 cells	Uterus	Homo sapiens (Human)	CVCL_9389
	HCE1 cells	Uterus	Homo sapiens (Human)	CVCL_A8SM
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	CASC2 upregulated PTEN expression by direct inhibiting miR21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AkT protein, CASC2 up-regulates PTEN as a ceRNA of miR21. Inhibiting miR21 increased the sensitivity of human glioblastoma cells U251 and LN229 to taxol.
Key Molecule: Growth arrest specific 5 (GAS5)				[6]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Activation	hsa04151
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The low level of GAS5 can down-regulate PTEN by interacting with miR21 because PTEN is one of the genes in the PI3k/Akt/mTOR pathway that can be regulated by GAS5 negatively. The low expression of PTEN activates the PI3k/Akt pathway.
Key Molecule: Urothelial cancer associated 1 (UCA1)				[7]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	HeLa/DDP cells	Uterus	Homo sapiens (Human)	CVCL_C869
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; EdU assay; Flow cytometric analysis
Mechanism Description	Overexpression of UCA1 confers cisplatin resistance by promoting cancer cell proliferation, migration, and invasion and inhibiting apoptosis.
Key Molecule: hsa-miR-7-5p				[8]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	There was a protective role of miR-7-5p in cervical cancer cells treated with cisplatin and that miR-7-5p expression.miR-7-5p reduced energy consumption via inhibiting PARP-1 expression, and miR-7-5p increased energy generation by suppressing the expression of Bcl-2.
Key Molecule: hsa-mir-181a				[9]
Resistant Disease	Cervical squamous cell carcinoma [ICD-11: 2C77.3]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The down-regulation of PRkCD expression may be a molecular mechanism through which miR-181a exerts its functions as an oncogene and an enhancer of chemoresistance to cisplatin in cervical squamous cell carcinoma cells.
Key Molecule: hsa-mir-200b				[10]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Clonogenic assay
Mechanism Description	The transcription factor AP-2alpha functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2alpha, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. miR-200b/200c/429 family recognized the MRE in the 3' UTR of AP-2alpha gene and negatively regulated the expression of endogenous AP-2alpha proteins.
Key Molecule: hsa-mir-200c				[10]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Clonogenic assay
Mechanism Description	The transcription factor AP-2alpha functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2alpha, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. miR-200b/200c/429 family recognized the MRE in the 3' UTR of AP-2alpha gene and negatively regulated the expression of endogenous AP-2alpha proteins.
Key Molecule: hsa-miR-429				[10]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Clonogenic assay
Mechanism Description	The transcription factor AP-2alpha functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2alpha, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. miR-200b/200c/429 family recognized the MRE in the 3' UTR of AP-2alpha gene and negatively regulated the expression of endogenous AP-2alpha proteins.
Key Molecule: hsa-let-7i				[11]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	Reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1)				[12]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	Cell viability		Activation	hsa05200
	HOXD/AS1/miR130a-3p/ZEB1 signaling pathway		Regulation	hsa05206
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	Western blot analysis; RIP assay; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Transwell assay
Mechanism Description	HOXD-AS1 enhanced chemoresistance of cisplatin-resistant CC cells by modulating miR-130a-3p/ZEB1 axis expression.
Key Molecule: HOXD antisense growth-associated long non-coding RNA (HAGLR)				[12]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell colony		Activation	hsa05200
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	Cell viability		Activation	hsa05200
	HOXD/AS1/miR130a-3p/ZEB1 signaling pathway		Regulation	hsa05206
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Transwell assay
Mechanism Description	HOXD-AS1 enhanced chemoresistance of cisplatin-resistant CC cells by modulating miR-130a-3p/ZEB1 axis expression.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Signal transducer activator transcription 3 (STAT3)				[4]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Phosphorylation		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	STAT3 signaling pathway		Activation	hsa04550
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description	Down-regulation of LncRNA GAS5 strengthen cisplatin-induced apoptosis in cervical cancer by regulating STAT3 signaling via miR-21.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[6]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K/AKT signaling pathway		Activation	hsa04151
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The low level of GAS5 can down-regulate PTEN by interacting with miR21 because PTEN is one of the genes in the PI3k/Akt/mTOR pathway that can be regulated by GAS5 negatively. The low expression of PTEN activates the PI3k/Akt pathway.
Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1)				[6]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	GAS5 knockdown (SiHa/cDDP-GAS5-siRNA) and SiHa cells with miR21 overexpression (SiHa/cDDP-miR21) had an up-regulated level of pAkt.
Key Molecule: Caspase-3 (CASP3)				[7]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	HeLa/DDP cells	Uterus	Homo sapiens (Human)	CVCL_C869
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; EdU assay; Flow cytometric analysis
Mechanism Description	UCA1 suppressed apoptosis by downregulating caspase 3 and upregulating CDk2, whereas enhanced cell proliferation by increased level of survivin and decreased level of p21.
Key Molecule: Cyclin-dependent kinase 2 (CDK2)				[7]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	HeLa/DDP cells	Uterus	Homo sapiens (Human)	CVCL_C869
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; EdU assay; Flow cytometric analysis
Mechanism Description	UCA1 suppressed apoptosis by downregulating caspase 3 and upregulating CDk2, whereas enhanced cell proliferation by increased level of survivin and decreased level of p21.
Key Molecule: Cyclin-dependent kinase inhibitor 1A (CDKN1A)				[7]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	HeLa/DDP cells	Uterus	Homo sapiens (Human)	CVCL_C869
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; EdU assay; Flow cytometric analysis
Mechanism Description	UCA1 suppressed apoptosis by downregulating caspase 3 and upregulating CDk2, whereas enhanced cell proliferation by increased level of survivin and decreased level of p21.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2)				[8]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	There was a protective role of miR-7-5p in cervical cancer cells treated with cisplatin and that miR-7-5p expression.miR-7-5p reduced energy consumption via inhibiting PARP-1 expression, and miR-7-5p increased energy generation by suppressing the expression of Bcl-2.
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1)				[8]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	There was a protective role of miR-7-5p in cervical cancer cells treated with cisplatin and that miR-7-5p expression.miR-7-5p reduced energy consumption via inhibiting PARP-1 expression, and miR-7-5p increased energy generation by suppressing the expression of Bcl-2.
Key Molecule: Protein kinase C delta type (PRKCD)				[9]
Resistant Disease	Cervical squamous cell carcinoma [ICD-11: 2C77.3]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	The down-regulation of PRkCD expression may be a molecular mechanism through which miR-181a exerts its functions as an oncogene and an enhancer of chemoresistance to cisplatin in cervical squamous cell carcinoma cells.
Key Molecule: Transcription factor AP2 alpha (TFAP2A)				[10]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Clonogenic assay
Mechanism Description	The transcription factor AP-2alpha functions as a tumor suppressor by regulating various genes that are involved in cell proliferation and apoptosis. Chemotherapeutic drugs including cisplatin induce post-transcriptionally endogenous AP-2alpha, which contributes to chemosensitivity by enhancing therapy-induced apoptosis. miR-200b/200c/429 family recognized the MRE in the 3' UTR of AP-2alpha gene and negatively regulated the expression of endogenous AP-2alpha proteins.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: NCK1 divergent transcript (NCK1-DT)				[13]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Silencing of NCk1-AS1 and upregulation of miR-134-5p promote HeLa cell apoptosis and reduce cisplatin resistance in cervical cancer cells.
Key Molecule: hsa-miR-134-5p				[13]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	Silencing of NCk1-AS1 and upregulation of miR-134-5p promote HeLa cell apoptosis and reduce cisplatin resistance in cervical cancer cells.
Key Molecule: Cancer susceptibility 2 (CASC2)				[5]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PTEN signaling pathway		Activation	hsa05235
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
	H8 cells	Uterus	Homo sapiens (Human)	CVCL_9389
	HCE1 cells	Uterus	Homo sapiens (Human)	CVCL_A8SM
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	CASC2 upregulated PTEN expression by direct inhibiting miR21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AkT protein, CASC2 up-regulates PTEN as a ceRNA of miR21. Inhibiting miR21 increased the sensitivity of human glioblastoma cells U251 and LN229 to taxol.
Key Molecule: hsa-mir-21				[5]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PTEN signaling pathway		Activation	hsa05235
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
	H8 cells	Uterus	Homo sapiens (Human)	CVCL_9389
	HCE1 cells	Uterus	Homo sapiens (Human)	CVCL_A8SM
Experiment for Molecule Alteration	qRT-PCR; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	CASC2 upregulated PTEN expression by direct inhibiting miR21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AkT protein, CASC2 up-regulates PTEN as a ceRNA of miR21. Inhibiting miR21 increased the sensitivity of human glioblastoma cells U251 and LN229 to taxol.
Key Molecule: hsa-miR-1284				[14]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug 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
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
	MS751 cells	Cervical	Homo sapiens (Human)	CVCL_4996
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Transwell assay
Mechanism Description	miR-1284 enhances sensitivity of cervical cancer cells to cisplatin via downregulating HMGB1.
Key Molecule: hsa-mir-103				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-miR-107				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-mir-218				[16]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/mTOR signaling pathway		Inhibition	hsa04150
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	PCR
Experiment for Drug Resistance	WST assay
Mechanism Description	Overexpression of miR-218 Inhibited Expression of Rictor, an mTOR Component, and Its Downstream Pathway, inhibited the proliferation of the human cervical cancer cell line HeLa and increased chemosensitivity to cisplatin in vitro by blocking the AkT-mTOR signaling pathway.
Key Molecule: hsa-mir-214				[17]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-214 significantly reduced cell survival and rendered cell sensitivity to cisplatin through inhibiting the anti-apoptotic protein Bcl2l2.
Key Molecule: hsa-mir-96				[18]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.
Key Molecule: hsa-mir-30a				[19]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-30a can sensitize tumor cells to cis-DDP via reducing beclin 1-mediated autophagy.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: Forkhead box protein M1 (FOXM1)				[20]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	Immunohistochemistry; Western blot analysis; qRT-PCR
Experiment for Drug Resistance	Wound healing assay; Transwell invasion assay; MTT assay
Mechanism Description	miR214 inhibits cell migration, invasion and promotes the drug sensitivity in human cervical cancer by targeting FOXM1. FOXM1 overexpression counteracts miR214 in cervical cancer, overexpression of FOXM1 reversed the inhibition in cell invasion caused by miR214 as well as the process of EMT, and neutralized the promotion of drug sensitivity to cisplatin that was induced by miR214.
Key Molecule: hsa-mir-214				[20]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Chemosensitivity		Activation	hsa05207
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Wound healing assay; Transwell invasion assay; MTT assay
Mechanism Description	miR214 inhibits cell migration, invasion and promotes the drug sensitivity in human cervical cancer by targeting FOXM1. FOXM1 overexpression counteracts miR214 in cervical cancer, overexpression of FOXM1 reversed the inhibition in cell invasion caused by miR214 as well as the process of EMT, and neutralized the promotion of drug sensitivity to cisplatin that was induced by miR214.
Key Molecule: hsa-mir-155				[21]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR155 reversed EGF-induced EMT by downregulating SMAD2 expression levels, and restraining cell growth by inhibiting CCND1 expression, increased the Chemo-sensitivity of Caski Cells to DDP.
Key Molecule: Mothers against decapentaplegic homolog 2 (SMAD2)				[21]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR155 reversed EGF-induced EMT by downregulating SMAD2 expression levels, and restraining cell growth by inhibiting CCND1 expression, increased the Chemo-sensitivity of Caski Cells to DDP.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4)				[4]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell migration		Activation	hsa04670
	Cell proliferation		Activation	hsa05200
	STAT3 signaling pathway		Activation	hsa04550
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description	Down-regulation of LncRNA GAS5 can suppress TIMP3 and PDCD4 expression by enhancing miR-21 expression to suppress apoptosis and promote migration, invasion and cisplatin resistance in cervical cancer through the STAT3 signaling pathway.
Key Molecule: Metalloproteinase inhibitor 3 (TIMP3)				[4]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
	Cell migration		Activation	hsa04670
	STAT3 signaling pathway		Activation	hsa04550
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis; RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay; Colony formation assay
Mechanism Description	Down-regulation of LncRNA GAS5 can suppress TIMP3 and PDCD4 expression by enhancing miR-21 expression to suppress apoptosis and promote migration, invasion and cisplatin resistance in cervical cancer through the STAT3 signaling pathway.
Key Molecule: DNA mismatch repair protein Msh2 (MSH2)				[13]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blot analysis; qRT-PCR
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay
Mechanism Description	NCk1-AS1 downregulation and miR-134-5p upregulation suppress the expression of MSH2 and reduce cisplatin resistance in cervical cancer cells.
Key Molecule: Phosphatase and tensin homolog (PTEN)				[5]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
	H8 cells	Uterus	Homo sapiens (Human)	CVCL_9389
	HCE1 cells	Uterus	Homo sapiens (Human)	CVCL_A8SM
Experiment for Molecule Alteration	Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	CASC2 upregulated PTEN expression by direct inhibiting miR21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AkT protein, CASC2 up-regulates PTEN as a ceRNA of miR21. Inhibiting miR21 increased the sensitivity of human glioblastoma cells U251 and LN229 to taxol.
Key Molecule: High mobility group protein B1 (HMGB1)				[14]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug 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 viability		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
	MS751 cells	Cervical	Homo sapiens (Human)	CVCL_4996
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay; Flow cytometry assay; Transwell assay
Mechanism Description	miR-1284 enhances sensitivity of cervical cancer cells to cisplatin via downregulating HMGB1.
Key Molecule: Pvt1 oncogene (PVT1)				[22]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	DoTc2 4510 cells	Cervix uteri	Homo sapiens (Human)	CVCL_1181
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Transwell assay
Mechanism Description	PVT1 knockdown by either siRNA or LNA oligonucleotides leads to increased responsiveness of SiHa cells to cisplatin.
Key Molecule: DNA repair protein RAD51 homolog 4 (RAD51D)				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: Rapamycin-insensitive companion of mTOR (RICTOR)				[16]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	AKT/mTOR signaling pathway		Inhibition	hsa04150
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	WST assay
Mechanism Description	Overexpression of miR-218 Inhibited Expression of Rictor, an mTOR Component, and Its Downstream Pathway, inhibited the proliferation of the human cervical cancer cell line HeLa and increased chemosensitivity to cisplatin in vitro by blocking the AkT-mTOR signaling pathway.
Key Molecule: Bcl-2-like protein 2 (BCL2L2)				[17]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-214 significantly reduced cell survival and rendered cell sensitivity to cisplatin through inhibiting the anti-apoptotic protein Bcl2l2.
Key Molecule: G1/S-specific cyclin-D1 (CCND1)				[21]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR155 reversed EGF-induced EMT by downregulating SMAD2 expression levels, and restraining cell growth by inhibiting CCND1 expression, increased the Chemo-sensitivity of Caski Cells to DDP.
Key Molecule: Transcription factor 4 (TCF4)				[21]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR155 reversed EGF-induced EMT by downregulating SMAD2 expression levels, and restraining cell growth by inhibiting CCND1 expression, increased the Chemo-sensitivity of Caski Cells to DDP.
Key Molecule: DNA repair protein REV1 (REV1)				[18]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	Overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.
Key Molecule: Beclin-1 (BECN1)				[19]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Cisplatin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Flow cytometry assay
Mechanism Description	miR-30a can sensitize tumor cells to cis-DDP via reducing beclin 1-mediated autophagy.

Cloperastine

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)			Click to Show/Hide
Key Molecule: Histamine receptor H1 (HRH1)				[23]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Function		Inhibition	Molecule Info
Sensitive Drug	Cloperastine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	SW480 cells	Colon	Homo sapiens (Human)	CVCL_0546
Experiment for Molecule Alteration	Quantitative RT-PCR assay
Experiment for Drug Resistance	CCK-8 assay; Flow cytometric analysis
Mechanism Description	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells. Here we show that cloperastine and two other histamine H1 receptor antagonists selectively kill HeLa cisR cells at concentrations that little affect parental HeLa S cells.

Docetaxel

Click to Show/Hide

Drug Resistance 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)				[24]
Resistant Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Docetaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Athymic nu/nu female mice xenograft model			Mus musculus
Experiment for Drug Resistance	MTS assay
Mechanism Description	In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Doxorubicin

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)			Click to Show/Hide
Key Molecule: Cytochrome P450 family 3 subfamily A member1 (CYP3A4)				[25]
Sensitive Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	CYP450-Glo CYP 3A4 assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	In this study, resveratrol was a significant inhibitor of CYP3A4 enzyme activity with IC50 value 9.32 ( M). Moreover, the CYP3A4 mRNA levels were reduced after treatment with resveratrol 0.03-fold of the control levels with high significance (p < 0.001).
Key Molecule: Glutathione S-transferase (GST)				[25]
Sensitive Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Glutathione-S-transferase assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	The Glutathione-S-transferases (GSTs) are a multigene family of dimeric proteins which play a central role in the detoxification of electrophilic xenobiotics and catalyze their conjugation with GSH to electrophilic metabolites, thus rendering them more water soluble. GSTs protect cells from cytotoxic and carcinogenic chemicals. GST activity was decreased by resveratrol in a dose dependent manner. IC50 value was 30.73 M. This results were confirmed by RT-PCR data, where the tested samples changed the GST mRNA level by 0.79-fold (p < 0.01) of control level.
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-135a				[26]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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 proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Promega viability kit assay
Mechanism Description	Down-regulated of FAk increased sensitivity of HeLa cancer cells to Fluorouracil chemotherapy, targeting and down-regulation of FAk expression by miR-135 and miR-138, overexpressed miR-138 and miR-135 had increased sensitivity to chemotherapy.
Key Molecule: hsa-mir-138				[26]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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 proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Promega viability kit assay
Mechanism Description	Down-regulated of FAk increased sensitivity of HeLa cancer cells to Fluorouracil chemotherapy, targeting and down-regulation of FAk expression by miR-135 and miR-138, overexpressed miR-138 and miR-135 had increased sensitivity to chemotherapy.
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5)				[25]
Sensitive Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Doxorubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Efflux of rhodamine123 assay
Experiment for Drug Resistance	MTT assay
Mechanism Description	Resveratrol can restore the sensitivity of Caco-2 and CEM/ADR5000 cell lines to doxorubicin, through enhancing significantly doxorubicin cytotoxicity. ABC-transporter inhibitors, classified according to their action on ABC-transporters proteins into: 1. Function inhibitors, 2. Expression inhibitors, and 3. Functional and expression inhibitors, which have an ideal characters of ABC-transporters inhibitors. Our results indicate that resveratrol falls into the class 3 inhibitors.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Focal adhesion kinase 1 (FAK1)				[26]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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 proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Promega viability kit assay
Mechanism Description	Down-regulated of FAk increased sensitivity of HeLa cancer cells to Fluorouracil chemotherapy, targeting and down-regulation of FAk expression by miR-135 and miR-138, overexpressed miR-138 and miR-135 had increased sensitivity to chemotherapy.

Etoposide

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-103				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-miR-107				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: DNA repair protein RAD51 homolog 1 (RAD51)				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: DNA repair protein RAD51 homolog 4 (RAD51D)				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Etoposide			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Fluorouracil

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-135a				[26]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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 proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Promega viability kit assay
Mechanism Description	Down-regulated of FAk increased sensitivity of HeLa cancer cells to Fluorouracil chemotherapy, targeting and down-regulation of FAk expression by miR-135 and miR-138, overexpressed miR-138 and miR-135 had increased sensitivity to chemotherapy.
Key Molecule: hsa-mir-138				[26]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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 proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Promega viability kit assay
Mechanism Description	Down-regulated of FAk increased sensitivity of HeLa cancer cells to Fluorouracil chemotherapy, targeting and down-regulation of FAk expression by miR-135 and miR-138, overexpressed miR-138 and miR-135 had increased sensitivity to chemotherapy.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Focal adhesion kinase 1 (FAK1)				[26]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
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 proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Promega viability kit assay
Mechanism Description	Down-regulated of FAk increased sensitivity of HeLa cancer cells to Fluorouracil chemotherapy, targeting and down-regulation of FAk expression by miR-135 and miR-138, overexpressed miR-138 and miR-135 had increased sensitivity to chemotherapy.

Metformin

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-142-3p				[27]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Demethylation		Up-regulation	Molecule Info
Sensitive Drug	Metformin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	Wound-healing assay; Transwell assay
Mechanism Description	Metformin inhibits the expression of MALAT1 and upregulates miR-142-3p in cervical cancer cells.
Key Molecule: Metastasis associated lung adenocarcinoma transcript 1 (MALAT1)				[27]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Metformin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Wound-healing assay; Transwell assay
Mechanism Description	Metformin inhibits the expression of MALAT1 and upregulates miR-142-3p in cervical cancer cells.

Mitomycin

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-145				[28]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Mitomycin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	p53 signaling pathway		Activation	hsa04115
In Vitro Model	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	RT-PCR; Northern blotting analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	p53 signalling pathway mediates the cytotoxic effects of chemotherapy, miR-145 augments p53-mediated cytotoxic effects.

Paclitaxel

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-375				[29]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	Paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial-mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial-mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells.
Key Molecule: hsa-mir-375				[30]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Activation	hsa05200
	Cell viability		Activation	hsa05200
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
In Vivo Model	BALB/c nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTS assay
Mechanism Description	Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo.
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: hsa-mir-195				[31]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	Flow cytometric analysis; CCK8 assay
Mechanism Description	LncRNA PVT1 epigenetically silences miR195 and modulates EMT and chemoresistance in cervical cancer cells. PVT1 could decrease miR195 expression via enhancing histone H3k27me3 in the miR195 promoter region and also via direct sponging of miR195.
Key Molecule: Pvt1 oncogene (PVT1)				[31]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Epithelial mesenchymal transition signaling pathway		Inhibition	hsa01521
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	Flow cytometric analysis; CCK8 assay
Mechanism Description	LncRNA PVT1 epigenetically silences miR195 and modulates EMT and chemoresistance in cervical cancer cells. PVT1 could decrease miR195 expression via enhancing histone H3k27me3 in the miR195 promoter region and also via direct sponging of miR195.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cadherin-1 (CDH1)				[29]
Resistant Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	Paclitaxel			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	Paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial-mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial-mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: Long non-protein coding RNA 511 (LINC00511)				[32]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell migration		Inhibition	hsa04670
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	LINC00511 knockdown prevents cervical cancer cell proliferation and reduces resistance to paclitaxel.
Key Molecule: hsa-mir-21				[33]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	PTEN/AKT signaling pathway		Regulation	hsa05235
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	Annexin V-FITC/PI staining for cell apoptosis assay; Hoechst 33258 staining for cell apoptosis assay; MTT assay
Mechanism Description	miR21 inhibitor suppresses cell proliferation and colony formation through regulating the PTEN/AkT pathway and improves paclitaxel sensitivity in cervical cancer cells.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Phosphatase and tensin homolog (PTEN)				[33]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Paclitaxel			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell proliferation		Activation	hsa05200
	PTEN/AKT signaling pathway		Regulation	hsa05235
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	ME-180 cells	Uterus	Homo sapiens (Human)	CVCL_1401
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	Annexin V-FITC/PI staining for cell apoptosis assay; Hoechst 33258 staining for cell apoptosis assay; MTT assay
Mechanism Description	miR21 inhibitor suppresses cell proliferation and colony formation through regulating the PTEN/AkT pathway and improves paclitaxel sensitivity in cervical cancer cells.

Pirarubicin

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-miR-34c-5p				[34]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Pirarubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR34C-5p/ATG4B-autophagy signaling pathway		Regulation	hsa05206
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	On the one side, THP induces apoptosis, which results in cell death. On the other side, THP activates the MIR34C-5p-ATG4B-autophagy signaling axis via the sequential triggering of MIR34C-5p downregulation, ATG4B mRNA stability enhancement, and ATG4B upregulation and autophagy induction. Moreover, autophagy protects cervical cancer cells from cell death. The autophagy inhibitor CQ sensitizes cervical cancer cells to THP treatment.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Cysteine protease ATG4B (ATG4B)				[34]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Pirarubicin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	miR34C-5p/ATG4B-autophagy signaling pathway		Regulation	hsa05206
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
In Vivo Model	Nude mouse xenograft model			Mus musculus
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	On the one side, THP induces apoptosis, which results in cell death. On the other side, THP activates the MIR34C-5p-ATG4B-autophagy signaling axis via the sequential triggering of MIR34C-5p downregulation, ATG4B mRNA stability enhancement, and ATG4B upregulation and autophagy induction. Moreover, autophagy protects cervical cancer cells from cell death. The autophagy inhibitor CQ sensitizes cervical cancer cells to THP treatment.

Propofol

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: HOX transcript antisense RNA (HOTAIR)				[35]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Propofol			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	mTOR/p70S6k signaling pathway		Inhibition	hsa04150
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase mTOR (mTOR)				[35]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Propofol			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell invasion		Inhibition	hsa05200
	Cell proliferation		Inhibition	hsa05200
	mTOR/p70S6k signaling pathway		Inhibition	hsa04150
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer.

Sirolimus

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-218				[36]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Sirolimus			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	mTOR signaling pathway		Inhibition	hsa04150
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
In Vivo Model	Mouse bearing cervical cancer model			Mus musculus
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	microRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor and reducing the level of Rictor in cervical cancer.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Rapamycin-insensitive companion of mTOR (RICTOR)				[36]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Sirolimus			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	mTOR signaling pathway		Inhibition	hsa04150
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
	C33A cells	Uterus	Homo sapiens (Human)	CVCL_1094
In Vivo Model	Mouse bearing cervical cancer model			Mus musculus
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; Flow cytometry assay
Mechanism Description	microRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor and reducing the level of Rictor in cervical cancer.

Vinblastine

Click to Show/Hide

Drug Resistance 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)				[24]
Resistant Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Vinblastine			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Athymic nu/nu female mice xenograft model			Mus musculus
Experiment for Drug Resistance	MTS assay
Mechanism Description	In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold.

Clinical Trial Drug(s)

3 drug(s) in total

Click to Show/Hide the Full List of Drugs

Camptothecin

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-103				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Camptothecin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-miR-107				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Camptothecin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	RT-PCR
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: DNA repair protein RAD51 homolog 1 (RAD51)				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Camptothecin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: DNA repair protein RAD51 homolog 4 (RAD51D)				[15]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Camptothecin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
	Cell proliferation		Inhibition	hsa05200
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	Survival assay/crystal violet staining assay
Mechanism Description	miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.

Capivasertib

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Aberration of the Drug's Therapeutic Target (ADTT)		Click to Show/Hide
Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1)			[37]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Missense mutation	p.E17K (c.49G>A)	Molecule Info
Sensitive Drug	Capivasertib		Drug Info
Experimental Note	Identified from the Human Clinical Data
In Vitro Model	Breast		.
Mechanism Description	The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Capivasertib by aberration of the drug's therapeutic target

TRAIL

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-942				[38]
Resistant Disease	Human papillomavirus-related endocervical adenocarcinoma [ICD-11: 2C77.2]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	TRAIL			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
In Vitro Model	BGC-823 cells	Gastric	Homo sapiens (Human)	CVCL_3360
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Interferon alpha-inducible protein 27 (IFI27)				[38]
Resistant Disease	Human papillomavirus-related endocervical adenocarcinoma [ICD-11: 2C77.2]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Resistant Drug	TRAIL			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Inhibition	hsa04210
	Cell invasion		Activation	hsa05200
In Vitro Model	BGC-823 cells	Gastric	Homo sapiens (Human)	CVCL_3360
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay
Mechanism Description	miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-126				[39]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	TRAIL			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	qRT-PCR
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer miR126 promotes TRAIL-induced apoptosis in TRAIL-resistant cervical cancer cells and increases the sensitivity of Hela-TR and SiHa-TR to TNF-alphaand FasL.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: CASP8 and FADD-like apoptosis regulator (CFLAR)				[39]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	TRAIL			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
Experiment for Molecule Alteration	Western blot analysis; Luciferase reporter assay
Experiment for Drug Resistance	CCK8 assay
Mechanism Description	miR126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer miR126 promotes TRAIL-induced apoptosis in TRAIL-resistant cervical cancer cells and increases the sensitivity of Hela-TR and SiHa-TR to TNF-alphaand FasL.

Discontinued Drug(s)

1 drug(s) in total

Click to Show/Hide the Full List of Drugs

Cevipabulin

Click to Show/Hide

Drug Resistance 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)				[24]
Resistant Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Cevipabulin			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
In Vivo Model	Athymic nu/nu female mice xenograft model			Mus musculus
Experiment for Drug Resistance	MTS assay
Mechanism Description	The compound was a weak substrate of multidrug resistance 1 (multidrug resistance transporter or P-glycoprotein). In a cell line expressing a high level of P-glycoprotein, the IC50 of TTI-237 increased 25-fold whereas those of paclitaxel and vincristine increased 806-fold and 925-fold, respectively.

Preclinical Drug(s)

1 drug(s) in total

Click to Show/Hide the Full List of Drugs

PW12

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Regulation by the Disease Microenvironment (RTDM)			Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA)				[40]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Missense mutation		p.E545K (c.1633G>A)	Molecule Info
Sensitive Drug	PW12			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Ba/F3 cells	Colon	Homo sapiens (Human)	CVCL_0161
Experiment for Molecule Alteration	Immunoblotting analysis
Experiment for Drug Resistance	MTS assay
Mechanism Description	The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of PW12 by aberration of the drug's therapeutic target

Investigative Drug(s)

4 drug(s) in total

Click to Show/Hide the Full List of Drugs

Benzenemethanol

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Epigenetic Alteration of DNA, RNA or Protein (EADR)			Click to Show/Hide
Key Molecule: hsa-mir-629				[41]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Benzenemethanol			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	RT-qPCR
Experiment for Drug Resistance	MTT assay; Annexin V/propidium iodide (PI) assay; Caspase 3/7 assay
Mechanism Description	Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1'S-1'-acetoxychavicol acetate via up-regulating RSU1. ACA downregulates miR629 expression and suppression of miR629 enhances sensitivity toward ACA, however, overexpression of miR629 did not cause significant differences in sensitivity toward ACA.
Unusual Activation of Pro-survival Pathway (UAPP)			Click to Show/Hide
Key Molecule: Ras suppressor protein 1 (RSU1)				[41]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Sensitive Drug	Benzenemethanol			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
Cell Pathway Regulation	Cell apoptosis		Activation	hsa04210
In Vitro Model	Siha cells	Cervix uteri	Homo sapiens (Human)	CVCL_0032
	Caski cells	Uterus	Homo sapiens (Human)	CVCL_1100
Experiment for Molecule Alteration	Western blot analysis
Experiment for Drug Resistance	MTT assay; Annexin V/propidium iodide (PI) assay; Caspase 3/7 assay
Mechanism Description	Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1'S-1'-acetoxychavicol acetate via up-regulating RSU1. ACA downregulates miR629 expression and suppression of miR629 enhances sensitivity toward ACA, however, overexpression of miR629 did not cause significant differences in sensitivity toward ACA.

Disorazole A1

Click to Show/Hide

Drug Resistance 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)				[42]
Resistant Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Disorazole A1			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	ArrayScan VTi imaging cytometer assay
Mechanism Description	Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Disorazole C1

Click to Show/Hide

Drug Resistance 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)				[42]
Resistant Disease	Cervical carcinoma [ICD-11: 2C77.1]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Disorazole C1			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Hela cells	Cervix uteri	Homo sapiens (Human)	CVCL_0030
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	ArrayScan VTi imaging cytometer assay
Mechanism Description	Compared with wild-type HeLa cells, disorazole C1-resistant HeLa/DZR cells were 34- and 8-fold resistant to disorazole C1 and disorazole A1 growth inhibition. HeLa/DZR cells expressed elevated levels of the drug resistance ATP-binding cassette ABCB1 transporter. The natural product disorazole A1 is not a substrate for the ABCB1 multiple drug resistance transporter. But at least a portion of the disorazole C1 and A1 resistance in HeLa/DZR was due to.

Gemcitabine/LY2780301

Click to Show/Hide

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Unusual Activation of Pro-survival Pathway (UAPP)		Click to Show/Hide
Key Molecule: PI3-kinase alpha (PIK3CA)			[43]
Sensitive Disease	Cervical cancer [ICD-11: 2C77.0]
Molecule Alteration	Missense mutation	p.E542K (c.1624G>A)	Molecule Info
Sensitive Drug	Gemcitabine/LY2780301		Drug Info
Experimental Note	Identified from the Human Clinical Data
Cell Pathway Regulation	PI3K signaling pathway	Inhibition	hsa04151

References

Ref 1	Baicalein inhibits cervical cancer progression via downregulating long noncoding RNA BDLNR and its downstream PI3K/Akt pathway. Int J Biochem Cell Biol. 2018 Jan;94:107-118. doi: 10.1016/j.biocel.2017.11.009. Epub 2017 Nov 23.
Ref 2	miR-126 Suppresses the proliferation of cervical cancer cells and alters cell sensitivity to the chemotherapeutic drug bleomycin. Asian Pac J Cancer Prev. 2014 Jan;14(11):6569-72. doi: 10.7314/apjcp.2013.14.11.6569.
Ref 3	MicroRNA-101 Suppresses Tumor Cell Proliferation by Acting as an Endogenous Proteasome Inhibitor via Targeting the Proteasome Assembly Factor POMP. Mol Cell. 2015 Jul 16;59(2):243-57. doi: 10.1016/j.molcel.2015.05.036. Epub 2015 Jul 2.
Ref 4	Growth arrest-specific 5 attenuates cisplatin-induced apoptosis in cervical cancer by regulating STAT3 signaling via miR-21. J Cell Physiol. 2019 Jun;234(6):9605-9615. doi: 10.1002/jcp.27647. Epub 2018 Oct 23.
Ref 5	Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin. Arch Biochem Biophys. 2017 Jun 1;623-624:20-30. doi: 10.1016/j.abb.2017.05.001. Epub 2017 May 8.
Ref 6	Long Noncoding RNA GAS5, Which Acts as a Tumor Suppressor via microRNA 21, Regulates Cisplatin Resistance Expression in Cervical Cancer. Int J Gynecol Cancer. 2017 Jul;27(6):1096-1108. doi: 10.1097/IGC.0000000000001028.
Ref 7	Expression of Long Noncoding RNA Urothelial Cancer Associated 1 Promotes Cisplatin Resistance in Cervical Cancer. Cancer Biother Radiopharm. 2017 Apr;32(3):101-110. doi: 10.1089/cbr.2016.2156.
Ref 8	MicroRNA-7-5p Promotes Cisplatin Resistance of Cervical Cancer Cells and Modulation of Cellular Energy Homeostasis by Regulating the Expression of the PARP-1 and BCL2 Genes. Med Sci Monit. 2018 Sep 16;24:6506-6516. doi: 10.12659/MSM.910969.
Ref 9	MicroRNA-181a enhances the chemoresistance of human cervical squamous cell carcinoma to cisplatin by targeting PRKCD. Exp Cell Res. 2014 Jan 1;320(1):12-20. doi: 10.1016/j.yexcr.2013.10.014. Epub 2013 Oct 31.
Ref 10	A miR-200b/200c/429-binding site polymorphism in the 3' untranslated region of the AP-2Alpha gene is associated with cisplatin resistance. PLoS One. 2011;6(12):e29043. doi: 10.1371/journal.pone.0029043. Epub 2011 Dec 14.
Ref 11	MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 2008 Dec 15;68(24):10307-14. doi: 10.1158/0008-5472.CAN-08-1954.
Ref 12	HOXD-AS1 Exerts Oncogenic Functions and Promotes Chemoresistance in Cisplatin-Resistant Cervical Cancer Cells. Hum Gene Ther. 2018 Dec;29(12):1438-1448. doi: 10.1089/hum.2017.256. Epub 2018 Sep 5.
Ref 13	Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to cisplatin in cervical cancer. J Cell Physiol. 2019 Apr;234(4):4302-4313. doi: 10.1002/jcp.27198. Epub 2018 Sep 17.
Ref 14	MiR-1284 enhances sensitivity of cervical cancer cells to cisplatin via downregulating HMGB1. Biomed Pharmacother. 2018 Nov;107:997-1003. doi: 10.1016/j.biopha.2018.08.059. Epub 2018 Aug 23.
Ref 15	Systematic screen identifies miRNAs that target RAD51 and RAD51D to enhance chemosensitivity. Mol Cancer Res. 2013 Dec;11(12):1564-73. doi: 10.1158/1541-7786.MCR-13-0292. Epub 2013 Oct 2.
Ref 16	MiR-218 impairs tumor growth and increases chemo-sensitivity to cisplatin in cervical cancer. Int J Mol Sci. 2012 Nov 28;13(12):16053-64. doi: 10.3390/ijms131216053.
Ref 17	MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett. 2013 Mar 1;587(5):488-95. doi: 10.1016/j.febslet.2013.01.016. Epub 2013 Jan 18.
Ref 18	MiR-96 downregulates REV1 and RAD51 to promote cellular sensitivity to cisplatin and PARP inhibition. Cancer Res. 2012 Aug 15;72(16):4037-46. doi: 10.1158/0008-5472.CAN-12-0103. Epub 2012 Jul 3.
Ref 19	MicroRNA-30a sensitizes tumor cells to cis-platinum via suppressing beclin 1-mediated autophagy. J Biol Chem. 2012 Feb 3;287(6):4148-56. doi: 10.1074/jbc.M111.307405. Epub 2011 Dec 8.
Ref 20	MiR-214 inhibits cell migration, invasion and promotes the drug sensitivity in human cervical cancer by targeting FOXM1. Am J Transl Res. 2017 Aug 15;9(8):3541-3557. eCollection 2017.
Ref 21	Up-regulated miR155 reverses the epithelial-mesenchymal transition induced by EGF and increases chemo-sensitivity to cisplatin in human Caski cervical cancer cells. PLoS One. 2012;7(12):e52310. doi: 10.1371/journal.pone.0052310. Epub 2012 Dec 20.
Ref 22	The lncRNA PVT1 Contributes to the Cervical Cancer Phenotype and Associates with Poor Patient Prognosis. PLoS One. 2016 May 27;11(5):e0156274. doi: 10.1371/journal.pone.0156274. eCollection 2016.
Ref 23	Histamine H1 receptor antagonists selectively kill cisplatin-resistant human cancer cells .Sci Rep. 2021 Jan 15;11(1):1492. doi: 10.1038/s41598-021-81077-y. 10.1038/s41598-021-81077-y
Ref 24	TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/0008-5472.CAN-07-1420.
Ref 25	Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine. 2019 Mar 1;55:269-281. doi: 10.1016/j.phymed.2018.06.046. Epub 2018 Jun 28.
Ref 26	MiR-138 and MiR-135 directly target focal adhesion kinase, inhibit cell invasion, and increase sensitivity to chemotherapy in cancer cells. Anticancer Agents Med Chem. 2014 Jan;14(1):18-28. doi: 10.2174/187152061401140108113435.
Ref 27	Metformin, a first-line drug for type 2 diabetes mellitus, disrupts the MALAT1/miR-142-3p sponge to decrease invasion and migration in cervical cancer cells. Eur J Pharmacol. 2018 Jul 5;830:59-67. doi: 10.1016/j.ejphar.2018.04.027. Epub 2018 Apr 25.
Ref 28	Glucocorticoid regulation of a novel HPV-E6-p53-miR-145 pathway modulates invasion and therapy resistance of cervical cancer cells. J Pathol. 2012 Oct;228(2):148-57. doi: 10.1002/path.3997. Epub 2012 Apr 18.
Ref 29	miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT. PLoS One. 2014 Oct 16;9(10):e109299. doi: 10.1371/journal.pone.0109299. eCollection 2014.
Ref 30	miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer. Br J Cancer. 2013 Jul 9;109(1):92-9. doi: 10.1038/bjc.2013.308. Epub 2013 Jun 18.
Ref 31	LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells. J Drug Target. 2017 Aug;25(7):637-644. doi: 10.1080/1061186X.2017.1307379. Epub 2017 Apr 3.
Ref 32	LINC00511 knockdown prevents cervical cancer cell proliferation and reduces resistance to paclitaxel. J Biosci. 2019 Jun;44(2):44.
Ref 33	miR-21 inhibitor suppresses cell proliferation and colony formation through regulating the PTEN/AKT pathway and improves paclitaxel sensitivity in cervical cancer cells. Mol Med Rep. 2017 May;15(5):2713-2719. doi: 10.3892/mmr.2017.6340. Epub 2017 Mar 16.
Ref 34	Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin. Autophagy. 2016 Jul 2;12(7):1105-17. doi: 10.1080/15548627.2016.1173798. Epub 2016 Apr 20.
Ref 35	Propofol promotes cell apoptosis via inhibiting HOTAIR mediated mTOR pathway in cervical cancer. Biochem Biophys Res Commun. 2015 Dec 25;468(4):561-7. doi: 10.1016/j.bbrc.2015.10.129. Epub 2015 Oct 31.
Ref 36	MicroRNA-218 increases cellular sensitivity to Rapamycin via targeting Rictor in cervical cancer. APMIS. 2015 Jul;123(7):562-70. doi: 10.1111/apm.12387. Epub 2015 Apr 24.
Ref 37	AKT Inhibition in Solid Tumors With AKT1 MutationsJ Clin Oncol. 2017 Jul 10;35(20):2251-2259. doi: 10.1200/JCO.2017.73.0143. Epub 2017 May 10.
Ref 38	miR-942 decreases TRAIL-induced apoptosis through ISG12a downregulation and is regulated by AKT. Oncotarget. 2014 Jul 15;5(13):4959-71. doi: 10.18632/oncotarget.2067.
Ref 39	MiR-126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer. Gene. 2017 Sep 5;627:420-427. doi: 10.1016/j.gene.2017.06.055. Epub 2017 Jun 29.
Ref 40	High levels of p110Delta PI3K expression in solid tumor cells suppress PTEN activity, generating cellular sensitivity to p110 Delta inhibitors through PTEN activationFASEB J. 2012 Jun;26(6):2498-508. doi: 10.1096/fj.11-198192. Epub 2012 Mar 5.
Ref 41	Suppression of microRNA-629 enhances sensitivity of cervical cancer cells to 1'S-1'-acetoxychavicol acetate via regulating RSU1. Onco Targets Ther. 2017 Mar 20;10:1695-1705. doi: 10.2147/OTT.S117492. eCollection 2017.
Ref 42	Identifying a resistance determinant for the antimitotic natural products disorazole C1 and A1. J Pharmacol Exp Ther. 2010 Mar;332(3):906-11. doi: 10.1124/jpet.109.162842. Epub 2009 Dec 15.
Ref 43	Safety, tolerability and antitumour activity of LY2780301 (p70S6K/AKT inhibitor) in combination with gemcitabine in molecularly selected patients with advanced or metastatic cancer: a phase IB dose escalation studyEur J Cancer. 2017 Sep;83:194-202. doi: 10.1016/j.ejca.2017.06.036. Epub 2017 Jul 24.

If you find any error in data or bug in web service, please kindly report it to Dr. Sun and Dr. Zhang.

Disease Information

Cite DRESIS

About

Correspondence

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