Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2017; 9(7): 268-280
Published online Jul 15, 2017. doi: 10.4251/wjgo.v9.i7.268
Emerging molecular targets and therapy for cholangiocarcinoma
Hamzeh Kayhanian, Elizabeth C Smyth, Chiara Braconi
Hamzeh Kayhanian, Elizabeth C Smyth, Chiara Braconi, Department of Gastrointestinal Oncology, Royal Marsden Hospital, London and Surrey SM2 5PT, United Kingdom
Chiara Braconi, Institute of Cancer Research, London and Surrey SM2 5PT, United Kingdom
Author contributions: Smyth EC and Braconi C should be as the co-corresponding authors; all authors wrote and edited the paper.
Conflict-of-interest statement: Smyth EC declares payment for advisory board participation from Five Prime Therapeutics and for an advisory role from Bristol Meyer-Squibb.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Elizabeth C Smyth, Department of Gastrointestinal Oncology, Royal Marsden Hospital, London and Surrey SM2 5PT, United Kingdom.
Telephone: +44-20-86426011 Fax: +44-20-86439414
Received: September 28, 2016
Peer-review started: October 7, 2016
First decision: December 1, 2016
Revised: January 5, 2017
Accepted: March 23, 2017
Article in press: March 24, 2017
Published online: July 15, 2017

Cholangiocarcinoma (CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients.

Keywords: Cholangiocarcinoma, Biliary tract cancer, Targeted therapy, Immunotherapy, Mutation, Molecular, Microenvironment, Stroma, MiRNA

Core tip: Cholangiocarcinoma (CCA) is a clinically challenging malignancy; it is rare, molecularly heterogenous and associated with a poor prognosis. Here we review recent data on the genomic landscape of CCA and highlight the results of clinical trials using targeted agents and immunotherapy. We find a number of promising therapeutic agents in development and discuss strategies to improve diagnosis and outcomes in this patient group.