The choice for the optimal therapy in advanced biliary tract cancers: Chemotherapy, targeted therapies or immunotherapy

Pharmacol Ther. 2020 Jun:210:107517. doi: 10.1016/j.pharmthera.2020.107517. Epub 2020 Feb 25.

Abstract

Biliary tract cancers (BTCs) represent a heterogeneous group that includes intrahepatic cholangiocarcinomas (CCAs), perihilar-CCAs or Klatskin tumors, extrahepatic-CCAs, and gallbladder adenocarcinoma. These entities have distinct demographics, risk factors, clinical presentation, and molecular characteristics. In advanced BTCs, the recommendations are mainly supporting a doublet chemotherapy regimen using cisplatin/gemcitabine (CisGem) with a 5-year overall survival rate close to 5% and median overall survival (mOS) of less than a year. The lack of overall efficacy stresses the need for personalized therapies. Recently, whole-genome and transcriptome sequencing highlighted the diversity of BTCs' subtypes. Distinct genetic alterations were retrieved according to the localization, with a high rate of potentially actionable alterations. Targeted therapies and immunotherapy have since then been tested for BTCs, trying to propose a more personalized treatment. This review describes the different therapeutic options, validated and in development, for patients with advanced BTCs.

Keywords: Biliary tract cancers; Cholangiocarcinoma; Genome sequencing; Immunotherapy; Targeted therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / immunology
  • Biliary Tract Neoplasms / mortality
  • Biliary Tract Neoplasms / therapy*
  • Biomarkers, Tumor / genetics
  • Clinical Decision-Making
  • Humans
  • Immunotherapy* / adverse effects
  • Immunotherapy* / mortality
  • Molecular Targeted Therapy* / adverse effects
  • Molecular Targeted Therapy* / mortality
  • Precision Medicine
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor