title: New genomic landscapes and therapeutic targets for biliary tract cancers.
abstract: Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms characterized by a dismal prognosis. At variance with most solid tumors, no effective molecular targeted agent has been currently approved for BTCs treatment and their molecular landscape has only been recently investigated. Comprehensive mutational profiling studies identified IDH1/2 and BAP1 as characteristic of intrahepatic cholangiocarcinomas, while extrahepatic cholangiocarcinomas and gallbladder carcinomas were characterized by frequent KRAS and TP53 alterations. Moreover, targeted next-generation sequencing has uncovered alterations in several key cellular pathways. BTC-specific alterations include disorders of major regulators of cell cycle and chromatin remodeling processes, as well as deregulation of the mTOR-, TGF-beta/Smad- and receptor tyrosine kinases signaling. The next step will be the correlation of these findings with clinical trials to identify predictive biomarkers for the development of personalized therapies. This will permit early access for BTC patients to innovative drugs.
authors.affiliation: ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro 2, 37134 Verona, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Simbolo
authors.affiliation: ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro 2, 37134 Verona, Italy, matteo.fassan@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mafficini
authors.affiliation: ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro.
authors.forename: Rita T
authors.initials: RT
authors.lastname: Lawlor
authors.affiliation: ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruzzenente
authors.affiliation: ARC-Net Research Centre, University and Hospital Trust of Verona, Piazzale L. Scuro.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D002470:Cell Survival; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents