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Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

1 Jan 2016Review

New genomic landscapes and therapeutic targets for biliary tract cancers

Michele Simbolo 1, Matteo Fassan 1,*, Andrea Mafficini 1, Rita T. Lawlor 2, Andrea Ruzzenente 3, Aldo Scarpa 2
Affiliations
Article Info

1 ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro 2, 37134 Verona, Italy

2 ARC-Net Research Centre and Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Piazzale L. Scuro 2, 37134 Verona, Italy

3 Department of Surgery and Oncology, University of Verona, Piazzale L. Scuro 2, 37134 Verona, Italy

Abstract

Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms characterized by a dismal prognosis. At variance with most solid tumors, no effective molecular targeted agent has been currently approved for BTCs treatment and their molecular landscape has only been recently investigated. Comprehensive mutational profiling studies identified IDH1/2 and BAP1 as characteristic of intrahepatic cholangiocarcinomas, while extrahepatic cholangiocarcinomas and gallbladder carcinomas were characterized by frequent KRAS and TP53 alterations. Moreover, targeted next-generation sequencing has uncovered alterations in several key cellular pathways. BTC-specific alterations include disorders of major regulators of cell cycle and chromatin remodeling processes, as well as deregulation of the mTOR-, TGF-beta/Smad- and receptor tyrosine kinases signaling. The next step will be the correlation of these findings with clinical trials to identify predictive biomarkers for the development of personalized therapies. This will permit early access for BTC patients to innovative drugs.

Keywords

  • Cholangiocarcinoma
  • Molecular Profiling
  • Targeted Therapy
  • Review

References