Molecular profiling of intrahepatic cholangiocarcinoma: the search for new therapeutic targets

Expert Rev Gastroenterol Hepatol. 2017 Apr;11(4):349-356. doi: 10.1080/17474124.2017.1292127. Epub 2017 Feb 13.

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary tumor of the liver and a highly lethal disease. Therapeutic options for advanced iCCA are limited and ineffective due to the largely incomplete understanding of the molecular pathogenesis of this deadly tumor. Areas covered: The present review article outlines the main studies and resulting discoveries on the molecular profiling of iCCA, with a special emphasis on the different techniques used for this purpose, the diagnostic and prognostic markers identified, as well as the genes and pathways that could be potentially targeted with innovative therapies. Expert commentary: Molecular profiling has led to the identification of distinct iCCA subtypes, characterized by peculiar genetic alterations and transcriptomic features. Targeted therapies against some of the identified genes are ongoing and hold great promise to improve the prognosis of iCCA patients.

Keywords: Intrahepatic cholangiocarcinoma (iCCA); molecular profiling; precision medicine; signaling pathways; therapeutic targets.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology
  • Drug Design*
  • Epigenesis, Genetic
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Molecular Targeted Therapy
  • Signal Transduction / drug effects
  • Transcriptome*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor