Signaling pathways as therapeutic targets in biliary tract cancer

Expert Opin Ther Targets. 2017 May;21(5):485-498. doi: 10.1080/14728222.2017.1306055. Epub 2017 Mar 17.

Abstract

The incidence of biliary tract cancer (BTC) is increasing, and the disease is frequently diagnosed during advanced stages, leading to poor overall survival. Limited treatment options are currently available and novel therapeutic approaches are needed. A number of completed clinical trials have evaluated the role of chemotherapy for BTC, demonstrating a marginal benefit. Thus, there is increased interest in applying targeted therapies for this disease. Areas covered: This review article summarizes the role of chemotherapeutic regimens for the treatment of BTC, and highlights key signal transduction pathways of interest for targeted inhibition. Of particular interest are the MEK or MAP2K (mitogen-activated protein kinase kinase), phosphatidylinositol-3 kinase (PI3K) and signal transducer and activator of transcription-3 (STAT3) pathways. We discuss the available data on several promising inhibitors of these pathways, both in the pre-clinical and clinical settings. Expert opinion: Future treatment strategies should address targeting of MEK, PI3K and STAT3 for BTC, with a focus on combined therapeutic approaches.

Keywords: Biliary tract cancer; MEK; PI3K; STAT3; cholangiocarcinoma; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / pathology
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Molecular Targeted Therapy*
  • Neoplasm Staging
  • Phosphoinositide-3 Kinase Inhibitors
  • STAT3 Transcription Factor / antagonists & inhibitors
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Mitogen-Activated Protein Kinase Kinases