Met, IGF1R, and Other New Targets in Upper GI Malignancies

• Published in: Current treatment options in oncology 2013-09, Vol.14 (3), p.321-336
• Main Authors: Popa, Elizabeta C., Shah, Manish A.
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - administration & dosage; Clinical Trials as Topic; Gastroenterology; Gastrointestinal Neoplasms - drug therapy; Gastrointestinal Neoplasms - genetics; Gastrointestinal Neoplasms - pathology; Humans; Medicine; Medicine & Public Health; Molecular Targeted Therapy; Oncology; Proto-Oncogene Proteins c-met - antagonists & inhibitors; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - immunology; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - immunology; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - immunology; Receptor, IGF Type 1 - antagonists & inhibitors; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - immunology; Section Editor; Signal Transduction - genetics; Upper Gastrointestinal Cancers (JD Berlin; Upper Gastrointestinal Tract - pathology
• ISSN: 1527-2729; 1534-6277; 1534-5277
• DOI: 10.1007/s11864-013-0245-5

Opinion statement 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.