Disease Information

General Information of the Disease (ID: DIS00206)

• Name: Biliary tract cancer
• ICD: ICD-11: 2C15

Type(s) of Resistant Mechanism of This Disease

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Midkine (MDK) [1]

• Resistant Disease: Biliary tract cancer [ICD-11: 2C15.0]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: GBC-SD cells; Gallbladder; Homo sapiens (Human); CVCL_6903
• In Vitro Model: RBE cells; Liver; Homo sapiens (Human); CVCL_4896
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK-8 assay
• Mechanism Description: BTC cell lines were more resistant to gemcitabine plus MDK compared with gemcitabine alone. In terms of the underlying mechanism, MDK promoted the epithelial to mesenchymal transition (EMT) of BTC cells and the enhancing effect of MDK on gemcitabine resistance was abrogated when the EMT was blocked with small interfering (si)RNA targeting Twist. In addition, MDK promoted the expression of Notch-1, while knockdown of Notch-1 by siRNA blocked the EMT process in the BTC cell lines.

Investigative Drug(s) 1 drug(s) in total

ERK inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Sensitive Disease: Biliary tract cancer [ICD-11: 2C15.0]
• Sensitive Drug: ERK inhibitors
• Molecule Alteration: Missense mutation; p.L485W (c.1799T>A)
• Experimental Note: Identified from the Human Clinical Data

References

• Ref 1: Effect of midkine on gemcitabine resistance in biliary tract cancer .Int J Mol Med. 2018 Apr;41(4):2003-2011. doi: 10.3892/ijmm.2018.3399. Epub 2018 Jan 18. 10.3892/ijmm.2018.3399
• Ref 2: Survival outcomes for various treatment modalities in advanced-stage grade 3 follicular lymphoma (FL3): A National Cancer Database (NCDB) study.