title: Development of molecularly targeted therapies in biliary tract cancers: reassessing the challenges and opportunities.
abstract: Biliary tract cancers (BTCs), which encompass intra- and extrahepatic cholangiocarcinomas as well as gallbladder carcinomas, are a genetically diverse collection of cancers. Most patients with BTC will present with unresectable or metastatic disease. Although the standard systemic chemotherapy approaches are emerging, the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. Recent early-stage clinical trials with targeted therapies appear promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here we summarize the relevant molecular pathogenesis, recent and ongoing clinical trials with targeted agents, and the key issues in clinical trial design in BTC.
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. azhu@partners.org
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Aram F
authors.initials: AF
authors.lastname: Hezel
mesh_terms: D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002945:Cisplatin; D000093542:Gemcitabine