Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges

Cancer Control. 2020 Jan-Dec;27(1):1073274820983013. doi: 10.1177/1073274820983013.

Abstract

Background: Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA).

Methods & results: In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials.

Conclusions: Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade. In this discouraging scenario, BRAF inhibition is currently emerging as a novel treatment option in patients harboring BRAF mutations.

Keywords: BRAF; biliary tract cancer; cholangiocarcinoma; dabrafenib; trametinib.

Publication types

  • Review

MeSH terms

  • Ampulla of Vater / pathology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bile Ducts / pathology
  • Biliary Tract Neoplasms / diagnosis
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / mortality
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / mortality
  • Gallbladder / pathology
  • Humans
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Mutation
  • Neoplasm Staging
  • Observational Studies as Topic
  • Prognosis
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
  • Proto-Oncogene Proteins B-raf / genetics
  • Randomized Controlled Trials as Topic

Substances

  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf