Targeted therapy for biliary tract cancers.
Biliary tract cancers (BTCs) are a heterogeneous group of malignancies, with a historically poor prognosis as a whole. Until recently, the development of effective therapeutics was hampered by the relatively low incidence, heterogeneity in patients and tumors, and correspondingly poor clinical trial enrollments. With the publication of the landmark phase III ABC-02 trial demonstrating the superiority of gemcitabine and cisplatin combination chemotherapy, the landscape changed for the development of new agents. Despite this progress, there are currently no approved targeted agents for BTC. This review will focus on recent developments in targeted therapeutics, directed against several key signaling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen-activated protein kinase pathway. Data from recent phase I and II trials will be discussed, along with a preview of upcoming trials involving targeted therapies.
Harvard Medical School, Tucker Gosnell Center for Gastrointestinal Cancers, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Yawkey 7E, Boston, MA 02114, USA. jfaris@partners.org
Jason E
JE
Faris
Andrew X
AX
Zhu
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D001650:Bile Duct Neoplasms / Q000188:drug therapy; D001653:Bile Ducts, Intrahepatic; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000068818:Cetuximab; D018281:Cholangiocarcinoma / Q000188:drug therapy; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005706:Gallbladder Neoplasms / Q000188:drug therapy; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D000077544:Panitumumab; D010671:Phenylurea Compounds; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000187:drug effects; D011725:Pyridines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D015398:Signal Transduction; D000077157:Sorafenib; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D000068258:Bevacizumab; D000068818:Cetuximab; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D000069347:Erlotinib Hydrochloride; D020928:Mitogen-Activated Protein Kinases; D009536:Niacinamide; D000077544:Panitumumab; D010671:Phenylurea Compounds; D019869:Phosphatidylinositol 3-Kinases; D048493:Proto-Oncogene Proteins B-raf; D011725:Pyridines; D011799:Quinazolines; D000077157:Sorafenib; D058570:TOR Serine-Threonine Kinases; C484760:PIK3CA protein, human