Disease Information

General Information of the Disease (ID: DIS00093)
Name
Endometrial cancer
ICD
ICD-11: 2C76
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  ADTT: Aberration of the Drug's Therapeutic Target
  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)
8 drug(s) in total
Click to Show/Hide the Full List of Drugs
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: hsa-mir-200b [1]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
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 [1]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
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 [1]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
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.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
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 autophagy Inhibition hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
Key Molecule: Multidrug resistance protein 3 (ABCB4) [2]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
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 autophagy Inhibition hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Beclin-1 (BECN1) [2]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
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 autophagy Inhibition hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
Key Molecule: Transcription factor AP2 alpha (TFAP2A) [1]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
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: HOX transcript antisense RNA (HOTAIR) [2]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell autophagy Activation hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
Key Molecule: hsa-mir-23b [3]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
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
Cell proliferation Inhibition hsa05200
In Vitro Model HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
Human normal endometrial epithelial cell line Uterus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 RNA pull-down assay; qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Long non-coding RNA TUSC7 acted as a potential tumor suppressor gene to inhibit cell growth as well as advance the chemotherapy sensitivity through targeted silencing of miR23b.
Key Molecule: Tumor suppressor candidate 7 (TUSC7) [3]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
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 Inhibition hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
Human normal endometrial epithelial cell line Uterus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Long non-coding RNA TUSC7 acted as a potential tumor suppressor gene to inhibit cell growth as well as advance the chemotherapy sensitivity through targeted silencing of miR23b.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein (MDR) [2]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell autophagy Activation hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [2]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell autophagy Activation hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Beclin-1 (BECN1) [2]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Cisplatin
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell autophagy Activation hsa04140
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Dual-color autophagy reporter assay; CCK8 assay; Flow cytometric analysis
Mechanism Description HOTAIR can regulate the cisplatin-resistance ability of human endometrial cancer cells through the regulation of autophagy by increasing Beclin-1, MDR, and P-gp expression.
Docetaxel
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Polycomb complex protein BMI-1 (BMI1) [4]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Mutation
.
 Molecule Info 
Resistant Drug Docetaxel
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation PI3K/AKT signaling pathway Activation hsa04151
Experiment for
Molecule Alteration		 Low throughput experiment assay
Experiment for
Drug Resistance		 Disease-free survival analysis
Mechanism Description Recently, Dong et al. demonstrated that loss of BMI1 in endometrial cancer cells reduces expression of drug resistance gene MRP1, suggesting that BMI1 is required for the drug resistance. Overexpression of BMI1 rescues tumor cells from the apoptosis induced by Okadaic acid and Epigallocatechin-3-gallate, well-known apoptotic agents.
Epothilone B
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: hsa-mir-200c [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: BDNF/NT-3 growth factors receptor (NTRK2) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Protein quaking (QKI) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Zinc finger E-box-binding homeobox 2 (ZEB2) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibronectin (FN1) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Tubulin beta-3 chain (TUBB3) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Epothilone B
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Medroxyprogesterone
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Progesterone receptor (PGR) [6]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Medroxyprogesterone
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SR786 cells Pleural effusion Homo sapiens (Human) CVCL_1711
IshikawaPR cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 RTPCR
Mechanism Description The presence of the progesterone receptor (PR) is the precondition for progesterone response and PR is a predictive marker for response of progesterone. Progesterone binds to its receptor PR-A and PR-B, subsequently inhibiting tumor growth and promoting tumor apoptosis by regulating downstream genes. Constant stimulation of progesterone reduced the expression of PGR and promoted the development of drug resistance. Thus, downregulation of PR especially PRB must be involved in progesterone resistance. However, the molecular mechanism of PGR dysfunction remains unclear.
Medroxyprogesterone acetate
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: Long non-protein coding RNA (LNC-CETP-3) [7]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Up-regulation
Expression
 Molecule Info 
Resistant Drug Medroxyprogesterone acetate
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
KLE cells Ovary Homo sapiens (Human) CVCL_1329
Experiment for
Molecule Alteration		 Microarray assay; qRT-PCR
Mechanism Description Medroxyprogesterone acetate causes the alterations of endoplasmic reticulum related mRNAs and LncRNAs in endometrial cancer cells.
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: Long non-protein coding RNA 672 (LINC00672) [8]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Paclitaxel
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model 293T cells Breast Homo sapiens (Human) CVCL_0063
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Transwell migration assay; Matrigel invasion assay; Flow cytometry assay; TUNEL assay; Wound healing assay; Colony formation assay
Mechanism Description LINC00672 can down-regulate LASP1 expression as a locus-restricted cofactor for p53-mediated gene suppression, thus impacting EC malig.ncies and chemosensitivity to paclitaxel.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: LIM and SH3 domain protein 1 (LASP1) [8]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Drug Paclitaxel
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model 293T cells Breast Homo sapiens (Human) CVCL_0063
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Transwell migration assay; Matrigel invasion assay; Flow cytometry assay; TUNEL assay; Wound healing assay; Colony formation assay
Mechanism Description LINC00672 can down-regulate LASP1 expression as a locus-restricted cofactor for p53-mediated gene suppression, thus impacting EC malig.ncies and chemosensitivity to paclitaxel.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-23b [3]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
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 Inhibition hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
Human normal endometrial epithelial cell line Uterus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 RNA pull-down assay; qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Long non-coding RNA TUSC7 acted as a potential tumor suppressor gene to inhibit cell growth as well as advance the chemotherapy sensitivity through targeted silencing of miR23b.
Key Molecule: Tumor suppressor candidate 7 (TUSC7) [3]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Paclitaxel
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
Human normal endometrial epithelial cell line Uterus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Long non-coding RNA TUSC7 acted as a potential tumor suppressor gene to inhibit cell growth as well as advance the chemotherapy sensitivity through targeted silencing of miR23b.
Key Molecule: hsa-miR-29c-3p [9]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Paclitaxel
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Inhibition hsa05200
Cell invasion Inhibition hsa05200
Cell viability Inhibition hsa05200
miR125a-5p/BCL2/MRP4 signaling pathway Regulation hsa05206
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The up-regulation of miR-29c-3p using exogenous mimic molecules markedly increased PTX sensitivity in both cell lines and reduced expression of kDM5B while the inhibitor of miR-29-3p resulted in the opposite effects.
Key Molecule: hsa-mir-24 [10]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Paclitaxel
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
In Vivo Model Crl:NU-Foxn1nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-24, which is under-expressed in EC, functions as a tumor-suppressing gene to inhibit malignant proliferation and advance chemotherapy sensitivity to paclitaxel in EC by targeted silencing of S100A8.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: hsa-mir-200c [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: BDNF/NT-3 growth factors receptor (NTRK2) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Protein quaking (QKI) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Zinc finger E-box-binding homeobox 2 (ZEB2) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Lysine-specific demethylase 5B (KDM5B) [9]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Paclitaxel
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Inhibition hsa05200
Cell invasion Inhibition hsa05200
Cell viability Inhibition hsa05200
miR125a-5p/BCL2/MRP4 signaling pathway Regulation hsa05206
In Vitro Model Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The up-regulation of miR-29c-3p using exogenous mimic molecules markedly increased PTX sensitivity in both cell lines and reduced expression of kDM5B while the inhibitor of miR-29-3p resulted in the opposite effects.
Key Molecule: Protein S100-A8 (S100A8) [10]
Sensitive Disease Endometrial carcinoma [ICD-11: 2C76.2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Paclitaxel
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model HEC-1A cells Uterus Homo sapiens (Human) CVCL_0293
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-24, which is under-expressed in EC, functions as a tumor-suppressing gene to inhibit malignant proliferation and advance chemotherapy sensitivity to paclitaxel in EC by targeted silencing of S100A8.
Key Molecule: Fibronectin (FN1) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Tubulin beta-3 chain (TUBB3) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
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 migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Progesterone
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: Nuclear paraspeckle assembly transcript 1 (NEAT1) [11]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Progesterone
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell cycle arrest Activation hsa04110
In Vitro Model 293T cells Breast Homo sapiens (Human) CVCL_0063
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Microarray
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Progesterone Repressed LncRNA NEAT1,LEF1, c-myc, and MMP9 in Wnt/beta-catenin Signaling Pathway via Inhibition of NEAT1/miRNA-146b-5p Axis in Endometrial Cancer.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Lymphoid enhancer-binding factor 1 (LEF1) [11]
Resistant Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Drug Progesterone
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell colony Activation hsa05200
Cell cycle Activation hsa04110
In Vitro Model 293T cells Breast Homo sapiens (Human) CVCL_0063
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description Progesterone Repressed LncRNA NEAT1,LEF1, c-myc, and MMP9 in Wnt/beta-catenin Signaling Pathway via Inhibition of NEAT1/miRNA-146b-5p Axis in Endometrial Cancer.
Vincristine
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: hsa-mir-200c [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: BDNF/NT-3 growth factors receptor (NTRK2) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Protein quaking (QKI) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Zinc finger E-box-binding homeobox 2 (ZEB2) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibronectin (FN1) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Key Molecule: Tubulin beta-3 chain (TUBB3) [5]
Sensitive Disease Endometrial cancer [ICD-11: 2C76.1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Drug Vincristine
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
In Vitro Model Hec50 cells Endometrium Homo sapiens (Human) CVCL_2929
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 ELISA assay
Mechanism Description Low or absent miR-200c results in aberrant expression of ZEB1 and consequent repression of E-cadherin. Reinstatement of miR-200c to such cells restores E-cadherin and dramatically reduces migration and invasion. One such gene, class IIIbeta-tubulin (TUBB3), which encodes a tubulin isotype normally found only in neuronal cells, is a direct target of miR-200c. Restoration of miR-200c increases sensitivity to microtubule-targeting agents by up to 85%. Since expression of TUBB3 is a common mechanism of resistance to microtubule-binding chemotherapeutic agents in many types of solid tumors, the ability of miR-200c to restore chemosensitivity to such agents may be explained by its ability to reduce TUBB3.
Clinical Trial Drug(s)
12 drug(s) in total
Click to Show/Hide the Full List of Drugs
Brivanib
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: Fibroblast growth factor receptor 2 (FGFR2) [12]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug Brivanib
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Brivanib by unusual activation of pro-survival pathway
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) [13]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Sensitive Drug Capivasertib
 Drug Info 
Experimental Note Identified from the Human Clinical Data
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
Key Molecule: RAC-alpha serine/threonine-protein kinase (AKT1) [14]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
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
Cediranib
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: Fibroblast growth factor receptor 2 (FGFR2) [12]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Sensitive Drug Cediranib
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.N549K (c.1647T>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [12]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug Cediranib
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SUP-M2 cells Colon Homo sapiens (Human) CVCL_2209
KARPAS-299 cells Peripheral blood Homo sapiens (Human) CVCL_1324
In Vivo Model mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of Cediranib by unusual activation of pro-survival pathway
Derazantinib
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: Fibroblast growth factor receptor 2 (FGFR2) [15]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug Derazantinib
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation FGF/FGFR signaling pathway Inhibition hsa01521
In Vitro Model A2780 cells Ovary Homo sapiens (Human) CVCL_0134
KG-1 cells Bone marrow Homo sapiens (Human) CVCL_0374
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
AN3CA cells Ovary Homo sapiens (Human) CVCL_0028
SkOV3 cells Ovary Homo sapiens (Human) CVCL_0532
K562 cells Blood Homo sapiens (Human) CVCL_0004
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
RT-112 cells Urinary bladder Homo sapiens (Human) CVCL_1670
MFM-223 cells Pleural effusion Homo sapiens (Human) CVCL_1408
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
COS-1 cells Kidney Chlorocebus aethiops (Green monkey) CVCL_0223
In Vivo Model SCID beige mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [15]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Sensitive Drug Derazantinib
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation FGF/FGFR signaling pathway Inhibition hsa01521
In Vitro Model A2780 cells Ovary Homo sapiens (Human) CVCL_0134
KG-1 cells Bone marrow Homo sapiens (Human) CVCL_0374
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
AN3CA cells Ovary Homo sapiens (Human) CVCL_0028
SkOV3 cells Ovary Homo sapiens (Human) CVCL_0532
K562 cells Blood Homo sapiens (Human) CVCL_0004
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
RT-112 cells Urinary bladder Homo sapiens (Human) CVCL_1670
MFM-223 cells Pleural effusion Homo sapiens (Human) CVCL_1408
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
COS-1 cells Kidney Chlorocebus aethiops (Green monkey) CVCL_0223
In Vivo Model SCID beige mouse PDX model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description In cells, inhibition of FGFR2 auto-phosphorylation and other proteins downstream in the FGFR pathway (FRS2alpha, AKT, ERK) was evident by the response to ARQ 087 treatment. Cell proliferation studies demonstrated ARQ 087 has anti-proliferative activity in cell lines driven by FGFR dysregulation, including amplifications, fusions, and mutations. Cell cycle studies in cell lines with high levels of FGFR2 protein showed a positive relationship between ARQ 087 induced G1 cell cycle arrest and subsequent induction of apoptosis. In addition, ARQ 087 was effective at inhibiting tumor growth in vivo in FGFR2 altered, SNU-16 and NCI-H716, xenograft tumor models with gene amplifications and fusions.
Selumetinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [16]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Resistant Drug Selumetinib
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blotting analysis
Experiment for
Drug Resistance		 CCK-8 assay
AZD-4547
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [17]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Resistant Drug AZD-4547
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
MOLM-1 cells Bone marrow Homo sapiens (Human) CVCL_2188
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
In Vivo Model Female balb/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Phospho-kinase array analysis; Reporter gene assay; Microarray analysis; RT-PCR; Gene set enrichment analysis
Experiment for
Drug Resistance		 MTT assay; Soft-agar colony assay
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [17]
Resistant Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N550K (c.1650T>G)
 Molecule Info 
Resistant Drug AZD-4547
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Ishikawa cells Endometrium Homo sapiens (Human) CVCL_2529
HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
MV4-11 cells Peripheral blood Homo sapiens (Human) CVCL_0064
TT cells Thyroid gland Homo sapiens (Human) CVCL_1774
MOLM-1 cells Bone marrow Homo sapiens (Human) CVCL_2188
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
In Vivo Model Female balb/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Phospho-kinase array analysis; Reporter gene assay; Microarray analysis; RT-PCR; Gene set enrichment analysis
Experiment for
Drug Resistance		 MTT assay; Soft-agar colony assay
DEBIO-1347
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: Fibroblast growth factor receptor 2 (FGFR2) [18]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug DEBIO-1347
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. . N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 CCK-8 assay
Key Molecule: Fibroblast growth factor receptor 2 (FGFR2) [18]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Sensitive Drug DEBIO-1347
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model 327 cells N.A. . N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 CCK-8 assay
Miransertib
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) [19]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Sensitive Drug Miransertib
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of Miransertib by aberration of the drug's therapeutic target
RO-5126766 free base
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: Fibroblast growth factor receptor 2 (FGFR2) [16]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug RO-5126766 free base
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
MkN-45 cells Gastric Homo sapiens (Human) CVCL_0434
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-N87 cells Gastric Homo sapiens (Human) CVCL_1603
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
KATO-3 cells Gastric Homo sapiens (Human) CVCL_0371
SNU-16 cells Gastric Homo sapiens (Human) CVCL_0076
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
RT-4 cells Urinary bladder Homo sapiens (Human) CVCL_0036
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
SUM-52PE cells Pleural effusion Homo sapiens (Human) CVCL_3425
NCI-H1581 cells Lung Homo sapiens (Human) CVCL_1479
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
MFE280 cells Endometrium Homo sapiens (Human) CVCL_1405
KMS-11 cells Pleural effusion Homo sapiens (Human) CVCL_2989
HSC-39 cells Ascites Homo sapiens (Human) CVCL_A385
DMS-114 cells Lung Homo sapiens (Human) CVCL_1174
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
KATO-III cells Pleural effusion Homo sapiens (Human) CVCL_0371
AN3 CA cells Endometrium Homo sapiens (Human) CVCL_0028
Experiment for
Molecule Alteration		 Microarray assay; Western blotting analysis
Experiment for
Drug Resistance		 CCK-8 assay
CH-5132799
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: PI3-kinase alpha (PIK3CA) [20]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.H1047Y (c.3139C>T)
 Molecule Info 
Sensitive Drug CH-5132799
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model KPL-4 cells Breast Homo sapiens (Human) CVCL_5310
IGROV1 cells Ovary Homo sapiens (Human) CVCL_1304
GXF97 cells N.A. . N.A.
In Vivo Model Female BALB-nu/nu mouse xenograft model Mus musculus
Experiment for
Drug Resistance		 CCK-8 assay
Mechanism Description The missense mutation p.H1047Y (c.3139C>T) in gene PIK3CA cause the sensitivity of CH-5132799 by aberration of the drug's therapeutic target
MTOR inhibitors
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 regulatory subunit beta (PIK3R2) [21]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N561D (c.1681A>G)
 Molecule Info 
Sensitive Drug MTOR inhibitors
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
Experiment for
Molecule Alteration		 Whole-gene resequencing assay
Mechanism Description The missense mutation p.N561D (c.1681A>G) in gene PIK3R2 cause the sensitivity of MTOR inhibitors by unusual activation of pro-survival pathway
Key Molecule: PI3-kinase regulatory subunit beta (PIK3R2) [21]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.A171V (c.512C>T)
 Molecule Info 
Sensitive Drug MTOR inhibitors
 Drug Info 
Experimental Note Identified from the Human Clinical Data
PRN1371
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: Fibroblast growth factor receptor 2 (FGFR2) [22]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Sensitive Drug PRN1371
 Drug Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation FGF/FGFR signaling pathway Inhibition hsa01521
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
NCI-H716 cells Colon Homo sapiens (Human) CVCL_1581
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
AN3CA cells Ovary Homo sapiens (Human) CVCL_0028
Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
SNU878 cells Liver Homo sapiens (Human) CVCL_5102
SNU16 cells Ascites Homo sapiens (Human) CVCL_0076
OPM2 cells Peripheral blood Homo sapiens (Human) CVCL_1625
LI7 cells Liver Homo sapiens (Human) CVCL_3840
JHH7 cells Liver Homo sapiens (Human) CVCL_2805
In Vivo Model Nude mouse PDX model Mus musculus
Experiment for
Drug Resistance		 Promega assay
Mechanism Description PRN1371 exhibits potent and durable pathway inhibition, and robust antiproliferative activity. PRN1371 demonstrates prolonged FGFR inhibition in vivo.
Preclinical Drug(s)
5 drug(s) in total
Click to Show/Hide the Full List of Drugs
ARQ 751
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) [19]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.E17K (c.49G>A)
 Molecule Info 
Sensitive Drug ARQ 751
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model DU-145 cells Prostate Homo sapiens (Human) CVCL_0105
LNCaP cells Prostate Homo sapiens (Human) CVCL_0395
MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
T47D cells Breast Homo sapiens (Human) CVCL_0553
NCI-H460 cells Lung Homo sapiens (Human) CVCL_0459
MDA-MB-453 cells Breast Homo sapiens (Human) CVCL_0418
MDA-MB-468 cells Breast Homo sapiens (Human) CVCL_0419
HCC70 cells Breast Homo sapiens (Human) CVCL_1270
A2058 cells Skin Homo sapiens (Human) CVCL_1059
Caco-2 cells Colon Homo sapiens (Human) CVCL_0025
MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
NCI-60 cells N.A. Homo sapiens (Human) N.A.
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
EVSA-T cells Ascites Homo sapiens (Human) CVCL_1207
CAL-120 cells Pleural effusion Homo sapiens (Human) CVCL_1104
BT-549 cells Breast Homo sapiens (Human) CVCL_1092
BT-474 cells Breast Homo sapiens (Human) CVCL_0179
BT-20 cells Mammary gland Homo sapiens (Human) CVCL_0178
B16F10 cells Skin Mus musculus (Mouse) CVCL_0159
In Vivo Model Female NMRI (nu/nu) mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Mechanism Description The missense mutation p.E17K (c.49G>A) in gene AKT1 cause the sensitivity of ARQ 751 by aberration of the drug's therapeutic target
E7090
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: Fibroblast growth factor receptor 2 (FGFR2) [23]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug E7090
 Drug Info 
Experimental Note Identified from the Human Clinical Data
FIIN-1
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: Fibroblast growth factor receptor 2 (FGFR2) [24]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N549K (c.1647T>G)
 Molecule Info 
Sensitive Drug FIIN-1
 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
Drug Resistance		 CellTiter-Glo Luminescent Cell Viability Assay
Mechanism Description The missense mutation p.N549K (c.1647T>G) in gene FGFR2 cause the sensitivity of FIIN-1 by aberration of the drug's therapeutic target
GSK3052230
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: Fibroblast growth factor receptor 2 (FGFR2) [25]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.S252W (c.755C>G)
 Molecule Info 
Sensitive Drug GSK3052230
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Lung .
Experiment for
Molecule Alteration		 QuantiGene Plex DNA assay
Mechanism Description The missense mutation p.S252W (c.755C>G) in gene FGFR2 cause the sensitivity of GSK3052230 by aberration of the drug's therapeutic target
Spliceostatin A
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: Splicing factor 3B subunit 1 (SF3B1) [26]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.K666N (c.1998G>C)
 Molecule Info 
Sensitive Drug Spliceostatin A
 Drug Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model PANC-1 cells Pancreas Homo sapiens (Human) CVCL_0480
Capan-1 cells Pancreas Homo sapiens (Human) CVCL_0237
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
HEC1A cells Uterus Homo sapiens (Human) CVCL_0293
Capan-1 cells Pancreas Homo sapiens (Human) CVCL_0237
Capan-2 cells Pancreas Homo sapiens (Human) CVCL_0026
Pancreatic Panc 0504 cells Pancreas Homo sapiens (Human) CVCL_1637
MFE296 cells Endometrium Homo sapiens (Human) CVCL_1406
HEC59 cells Endometrium Homo sapiens (Human) CVCL_2930
ESS-1 cells Endometrium Homo sapiens (Human) CVCL_1205
DSMZ cells N.A. . N.A.
ESS-1 cells Endometrium Homo sapiens (Human) CVCL_1205
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CellTiter-Glo assay
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
PD173074
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: Fibroblast growth factor receptor 2 (FGFR2) [27]
Sensitive Disease Endometrial adenocarcinoma [ICD-11: 2C76.0]
Molecule Alteration Missense mutation
p.N550K (c.1650T>A)
 Molecule Info 
Sensitive Drug PD173074
 Drug Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Uterus .
Experiment for
Molecule Alteration		 DNA sequencing assay
Experiment for
Drug Resistance		 Sulforhodamine B assay
Mechanism Description The missense mutation p.N550K (c.1650T>A) in gene FGFR2 cause the sensitivity of PD173074 by aberration of the drug's therapeutic target
References
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Ref 2 Autophagy regulated by lncRNA HOTAIR contributes to the cisplatin-induced resistance in endometrial cancer cells. Biotechnol Lett. 2017 Oct;39(10):1477-1484. doi: 10.1007/s10529-017-2392-4. Epub 2017 Jul 18.
Ref 3 Long non-coding RNA tumor suppressor candidate 7 advances chemotherapy sensitivity of endometrial carcinoma through targeted silencing of miR-23b. Tumour Biol. 2017 Jun;39(6):1010428317707883. doi: 10.1177/1010428317707883.
Ref 4 Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells. 2012 Mar;30(3):372-8. doi: 10.1002/stem.1035.
Ref 5 MicroRNA-200c mitigates invasiveness and restores sensitivity to microtubule-targeting chemotherapeutic agents. Mol Cancer Ther. 2009 May;8(5):1055-66. doi: 10.1158/1535-7163.MCT-08-1046. Epub 2009 May 12.
Ref 6 Comprehensive bioinformatics analysis of acquired progesterone resistance in endometrial cancer cell line .J Transl Med. 2019 Feb 27;17(1):58. doi: 10.1186/s12967-019-1814-6. 10.1186/s12967-019-1814-6
Ref 7 Medroxyprogesterone acetate causes the alterations of endoplasmic reticulum related mRNAs and lncRNAs in endometrial cancer cellsBMC Med Genomics. 2019 Nov 12;12(1):163. doi: 10.1186/s12920-019-0601-9.
Ref 8 Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity. J Biol Chem. 2017 Apr 7;292(14):5801-5813. doi: 10.1074/jbc.M116.758508. Epub 2017 Feb 23.
Ref 9 Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma. Gene. 2019 Apr 30;694:76-82. doi: 10.1016/j.gene.2018.12.076. Epub 2019 Jan 16.
Ref 10 Targeted Silencing of S100A8 Gene by miR-24 to Increase Chemotherapy Sensitivity of Endometrial Carcinoma Cells to Paclitaxel. Med Sci Monit. 2016 Jun 9;22:1953-8. doi: 10.12659/msm.899179.
Ref 11 Investigations on the mechanism of progesterone in inhibiting endometrial cancer cell cycle and viability via regulation of long noncoding RNA NEAT1/microRNA-146b-5p mediated Wnt/Beta-catenin signaling. IUBMB Life. 2019 Feb;71(2):223-234. doi: 10.1002/iub.1959. Epub 2018 Nov 19.
Ref 12 Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer modelsMol Cancer Ther. 2012 Mar;11(3):690-9. doi: 10.1158/1535-7163.MCT-11-0450. Epub 2012 Jan 11.
Ref 13 Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic backgroundMol Cancer Ther. 2012 Apr;11(4):873-87. doi: 10.1158/1535-7163.MCT-11-0824-T. Epub 2012 Jan 31.
Ref 14 Capivasertib Active against AKT1-Mutated CancersCancer Discov. 2019 Jan;9(1):OF7. doi: 10.1158/2159-8290.CD-NB2018-153. Epub 2018 Nov 14.
Ref 15 Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR DysregulationPLoS One. 2016 Sep 14;11(9):e0162594. doi: 10.1371/journal.pone.0162594. eCollection 2016.
Ref 16 ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR InhibitorMol Cancer Ther. 2015 Dec;14(12):2831-9. doi: 10.1158/1535-7163.MCT-15-0497. Epub 2015 Oct 5.
Ref 17 Antitumor Effects and Mechanisms of AZD4547 on FGFR2-Deregulated Endometrial Cancer CellsMol Cancer Ther. 2015 Oct;14(10):2292-302. doi: 10.1158/1535-7163.MCT-15-0032. Epub 2015 Aug 20.
Ref 18 The fibroblast growth factor receptor genetic status as a potential predictor of the sensitivity to CH5183284/Debio 1347, a novel selective FGFR inhibitorMol Cancer Ther. 2014 Nov;13(11):2547-58. doi: 10.1158/1535-7163.MCT-14-0248. Epub 2014 Aug 28.
Ref 19 Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092PLoS One. 2015 Oct 15;10(10):e0140479. doi: 10.1371/journal.pone.0140479. eCollection 2015.
Ref 20 The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutationsClin Cancer Res. 2011 May 15;17(10):3272-81. doi: 10.1158/1078-0432.CCR-10-2882. Epub 2011 May 10.
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Ref 22 The Irreversible Covalent Fibroblast Growth Factor Receptor Inhibitor PRN1371 Exhibits Sustained Inhibition of FGFR after Drug ClearanceMol Cancer Ther. 2017 Dec;16(12):2668-2676. doi: 10.1158/1535-7163.MCT-17-0309. Epub 2017 Oct 4.
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