title: Met, IGF1R, and other new targets in upper GI malignancies.
abstract: Upper gastrointestinal (GI) malignancies comprise some of the most aggressive human cancers. Expanding knowledge of molecular mechanisms is finally translating into clinical application, and this has occurred at a relatively rapid rate in the past several years. However, despite recent advances in targeted therapies in upper GI cancers our overall success with targeted therapeutics in this disease area remains dismal. This statement is particularly troubling given some sobering facts: upper GI malignancies are prevalent as well as aggressive with a high morbidity and mortality. Esophagus and gastric cancer combined have an annual global incidence of over 1.2 million new cases annually while median survival is less than 1 year for most patients with metastatic disease. Progress has been limited due to several factors including: disease heterogeneity and variance of phenotype across the globe, clinical trial design strategies that have not yet incorporated selective mechanisms to afford individualized matching of drug to tumor molecular profile and last, a lack of validated predictive markers. Nevertheless there is evidence that many targeted agents can be administered safely at doses that achieve the required effect at the protein level. Several drugs that have negative early trial results can be potentially vital therapeutic agents if patient selection is appropriate.
authors.affiliation: Division of Hematology and Medical Oncology, Weill Cornell Medical College, 1305 York Avenue 12th floor, New York, NY, 10021, USA, ecp2002@med.cornell.edu.
authors.forename: Elizabeta C
authors.initials: EC
authors.lastname: Popa
authors.forename: Manish A
authors.initials: MA
authors.lastname: Shah
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics; D041742:Upper Gastrointestinal Tract / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; C524459:rilotumumab; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C491743:MET protein, human