title: Signaling pathways as therapeutic targets in biliary tract cancer.
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.
authors.affiliation: a Molecular Cellular and Developmental Biology Graduate Program , The Ohio State University , Columbus , OH , USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Yang
authors.affiliation: b Department of Hematology and Medical Oncology , The Winship Cancer Institute of Emory University , Atlanta , GA , USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Farren
authors.affiliation: c Division of Medical Oncology, Department of Medicine , Mayo Clinic , Phoenix , AZ , USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ahn
authors.affiliation: c Division of Medical Oncology, Department of Medicine , Mayo Clinic , Phoenix , AZ , USA.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.affiliation: b Department of Hematology and Medical Oncology , The Winship Cancer Institute of Emory University , Atlanta , GA , USA.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Lesinski
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Biliary tract cancer; MEK; PI3K; STAT3; cholangiocarcinoma; targeted therapy