Signaling pathways as therapeutic targets in biliary tract cancer

• Type of Material: Article
• Authors: Jennifer Yang, Ohio State University; Matthew R. Farren, Emory University; Daniel Ahn, Mayo Clinic; Tanios Bekaii-Saab, Mayo Clinic; Gregory Lesinski, Emory University
• Language: English
• Date: 2017-05-01
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles - No Open Select
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Informa UK Limited, trading as Taylor & Francis Group.
• Final Published Version (URL): http://dx.doi.org/10.1080/14728222.2017.1306055
• Title of Journal or Parent Work: Expert Opinion on Therapeutic Targets
• ISSN: 1472-8222
• Volume: 21
• Issue: 5
• Start Page: 485
• End Page: 498
• Keywords: TUMOR-SUPPRESSOR GENE; STAT3; PI3K; PHASE-II TRIAL; PHOSPHOINOSITIDE 3-KINASE INHIBITION; PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; CELL LUNG-CANCER; Biliary tract cancer; Science & Technology; targeted therapy; ISOCITRATE DEHYDROGENASE 1; Life Sciences & Biomedicine; SINGLE-AGENT GEMCITABINE; ORAL MEK INHIBITOR; CAPECITABINE PLUS CISPLATIN; GROWTH-FACTOR RECEPTOR; MEK; Pharmacology & Pharmacy; cholangiocarcinoma
• Research Categories: Health Sciences, Oncology; Biology, Molecular

Abstract

Introduction: 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.