title: Genetics of biliary tract cancers and emerging targeted therapies.
abstract: Biliary tract cancers (BTC), which encompass intra- and extrahepatic cholangiocarcinomas and gallbladder carcinomas, are a genetically diverse collection of cancers. Evidence suggests distinct models of molecular and pathologic progression, and a growing body of genetics data points to a heterogeneous collection of underlying mutations in key oncogenes and tumor suppressor genes. Although tumor genetics have been used to tailor individual treatment regimens and guide clinical decision making in other cancers, these principles have not been applied in BTC. Recent clinical trials with targeted therapies seem promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here, we summarize the molecular pathogenesis and genetics of BTCs and animal modeling and relate these to recent and ongoing clinical trials with targeted agents.
authors.affiliation: James P Wilmot Cancer Center, University of Rochester School of Medicine, Rochester, NY 14642, USA. Aram_Hezel@URMC.Rochester.edu
authors.forename: Aram F
authors.initials: AF
authors.lastname: Hezel
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004195:Disease Models, Animal; D016147:Genes, Tumor Suppressor; D006801:Humans; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000502:physiology
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins