Cholangiocarcinoma: novel therapeutic targets

Expert Opin Ther Targets. 2020 Apr;24(4):345-357. doi: 10.1080/14728222.2020.1733528. Epub 2020 Feb 26.

Abstract

Introduction: Cholangiocarcinoma (CCA) is a liver cancer derived from the biliary tree with a less than 30% five-year survival rate. Early diagnosis of CCA is challenging and treatment options are limited. Some CCA patients have genetic mutations and several therapeutic drugs or antibodies have been introduced to target abnormally expressed proteins. However, CCA is heterogeneous and patients often present with drug resistance which is attributed to multiple mutations or other factors. Novel approaches and methodologies for CCA treatments are in demand.Area covered: This review summarizes current approaches for CCA treatments leading to the development of novel therapeutic drugs or tools for human CCA patients. A literature search was conducted in PubMed utilizing the combination of the searched term 'cholangiocarcinoma' with other keywords such as 'miRNA', 'FGFR', 'immunotherapy' or 'microenvironment'. Papers published within 2015-2019 were obtained for reading.Expert opinion: Preclinical studies have demonstrated promising therapeutic approaches that target various cells or pathways. Recent studies have revealed that hepatic cells coordinate to promote CCA tumor progression in the tumor microenvironment, which may be a new therapeutic target. Although further studies are required, novel therapeutic tools such as extracellular vesicles could be utilized to manage CCA and its microenvironment.

Keywords: Cholangiocarcinoma; extracellular vesicles; immunotherapy; long non-coding RNA; microRNA; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / pathology
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / pathology
  • Disease Progression
  • Drug Development
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Molecular Targeted Therapy*
  • Mutation
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents