Targeting cholangiocarcinoma

Joachim C. Mertens, Sumera Rizvi, Gregory James Gores

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cholangiocarcinoma (CCA) represents a diverse group of epithelial cancers associated with the biliary tract, and can best be stratified anatomically into intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) subsets. Molecular profiling has identified genetic aberrations associated with these anatomic subsets. For example, IDH catalytic site mutations and constitutively active FGFR2 fusion genes are predominantly identified in iCCA, whereas KRAS mutations and PRKACB fusions genes are identified in pCCA and dCCA. Clinical trials targeting these specific driver mutations are in progress. However, The Tumor Genome Atlas (TCGA) marker analysis of CCA also highlights the tremendous molecular heterogeneity of this cancer rendering comprehensive employment of targeted therapies challenging. CCA also display a rich tumor microenvironment which may be easier to target. For example, targeting cancer associated fibroblasts for apoptosis with BH3-mimetics and/or and reversing T-cell exhaustion with immune check point inhibitors may help aid in the treatment of this otherwise devastating malignancy. Combinatorial therapy attacking the tumor microenvironment plus targeted therapy may help advance treatment for CCA. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.

Original languageEnglish (US)
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
DOIs
StateAccepted/In press - 2017

Fingerprint

Cholangiocarcinoma
Tumor Microenvironment
Gene Fusion
Mutation
Neoplasms
Atlases
Biliary Tract
Catalytic Domain
Therapeutics
Clinical Trials
Genome
Apoptosis
T-Lymphocytes
Health

Keywords

  • Biliary tract cancer
  • Cholangiocarcinoma
  • Driver mutations
  • Microenvironment
  • Molecular targets

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Targeting cholangiocarcinoma. / Mertens, Joachim C.; Rizvi, Sumera; Gores, Gregory James.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, 2017.

Research output: Contribution to journalArticle

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