Disease Information

General Information of the Disease (ID: DIS00076)

• Name: Gallbladder cancer
• ICD: ICD-11: 2C13

Type(s) of Resistant Mechanism of This Disease

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-125b-5p [1]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR125b-5p/BCL2 signaling pathway; Regulation; hsa05206
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vitro Model: HEK293 FT cells; Kidney; Homo sapiens (Human); CVCL_6911
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTS assay; Annexin V/PI Apoptosis Detection assay
• Mechanism Description: miR125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer.

Key Molecule: hsa-mir-31 [2]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR31/Src/AKT/Bax/BCL2 signaling pathway; Inhibition; hsa05206
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vitro Model: GBC-SD/DDP cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ/DDP cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony forming assay
• Mechanism Description: miR31 regulates the cisplatin resistance by targeting Src in gallbladder cancer The Src/Akt/Bax/Bcl-2 signaling cascade could be activated in the miR31-downregulated DDP-resistant GBC cells, and downregulation of Src sensitized the miR31 expressing GBC cells to DDP.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [1]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR125b-5p/BCL2 signaling pathway; Regulation; hsa05206
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vitro Model: HEK293 FT cells; Kidney; Homo sapiens (Human); CVCL_6911
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Annexin V/PI Apoptosis Detection assay
• Mechanism Description: miR125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer.

Key Molecule: Proto-oncogene tyrosine-protein kinase Src (SRC) [2]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Cisplatin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: miR31/Src/AKT/Bax/BCL2 signaling pathway; Inhibition; hsa05206
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vitro Model: GBC-SD/DDP cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ/DDP cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony forming assay
• Mechanism Description: miR31 regulates the cisplatin resistance by targeting Src in gallbladder cancer The Src/Akt/Bax/Bcl-2 signaling cascade could be activated in the miR31-downregulated DDP-resistant GBC cells, and downregulation of Src sensitized the miR31 expressing GBC cells to DDP.

Docetaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-223 [3]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Stathmin (STMN1) [3]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Docetaxel
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Long non-protein coding RNA (GBCDRlnc1) [4]

• Resistant Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Up-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• Cell Pathway Regulation: GBCD/Rlnc1/PGK1 signaling pathway; Activation; hsa04066
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA GBCDRlnc1 induces autophagy and drug-resistance of gallbladder cancer cells by interacting with PGk1 and preventing its degradation, which eventually upregulates ATG5-ATG12 expression.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphoglycerate kinase 1 (PGK1) [4]

• Resistant Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Down-regulation
• Resistant Drug: Doxorubicin
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell autophagy; Activation; hsa04140
• Cell Pathway Regulation: GBCD/Rlnc1/PGK1 signaling pathway; Activation; hsa04066
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RNA immunoprecipitation; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: LncRNA GBCDRlnc1 induces autophagy and drug-resistance of gallbladder cancer cells by interacting with PGk1 and preventing its degradation, which eventually upregulates ATG5-ATG12 expression.

Gemcitabine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-218-5p [5]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Up-regulation
• Sensitive Drug: Gemcitabine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PRKCE/MDR1 signaling pathway; Inhibition; hsa05206
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vitro Model: SGC-996 cells; Gallbladder; Homo sapiens (Human); CVCL_M737
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTS assay; Annexin V assay
• Mechanism Description: miR218-5p restores sensitivity to gemcitabine through PRkCE/MDR1 axis in gallbladder cancer, miR218-5p promotes sensitivity of gemcitabine by abolishing PRkCE-induced upregulation of MDR1/P-gp.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Protein kinase C epsilon type (PRKCE) [5]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Expression; Down-regulation
• Sensitive Drug: Gemcitabine
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PRKCE/MDR1 signaling pathway; Inhibition; hsa05206
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: NOZ cells; Gallbladder; Homo sapiens (Human); CVCL_3079
• In Vitro Model: SGC-996 cells; Gallbladder; Homo sapiens (Human); CVCL_M737
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Immunoblot assay; Dual-luciferase reporter assay
• Experiment for Drug Resistance: MTS assay; Annexin V assay
• Mechanism Description: miR218-5p restores sensitivity to gemcitabine through PRkCE/MDR1 axis in gallbladder cancer, miR218-5p promotes sensitivity of gemcitabine by abolishing PRkCE-induced upregulation of MDR1/P-gp.

Clinical Trial Drug(s) 1 drug(s) in total

Ulixertinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [6]

• Sensitive Disease: Gallbladder cancer [ICD-11: 2C13.0]
• Molecule Alteration: Missense mutation; p.L485W (c.1454T>G)
• Sensitive Drug: Ulixertinib
• Experimental Note: Identified from the Human Clinical Data

References

• Ref 1: miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer. Sci Rep. 2017 Mar 3;7:43109. doi: 10.1038/srep43109.
• Ref 2: MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer. Oncotarget. 2016 Dec 13;7(50):83060-83070. doi: 10.18632/oncotarget.13067.
• Ref 3: miR-223 increases gallbladder cancer cell sensitivity to docetaxel by downregulating STMN1. Oncotarget. 2016 Sep 20;7(38):62364-62376. doi: 10.18632/oncotarget.11634.
• Ref 4: Long non-coding RNA GBCDRlnc1 induces chemoresistance of gallbladder cancer cells by activating autophagy. Mol Cancer. 2019 Apr 5;18(1):82. doi: 10.1186/s12943-019-1016-0.
• Ref 5: miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer. Cell Death Dis. 2017 May 11;8(5):e2770. doi: 10.1038/cddis.2017.178.
• Ref 6: First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion StudyCancer Discov. 2018 Feb;8(2):184-195. doi: 10.1158/2159-8290.CD-17-1119. Epub 2017 Dec 15.