title: Targeted Therapies for Advanced Oesophagogastric Cancer: Recent Progress and Future Directions.
abstract: The genomic landscape of oesophagogastric (OG) cancer is highly complex. The recent elucidation of some of the pathways involved has suggested a number of novel targets for therapy. This therapy is urgently required as with conventional chemotherapy regimens patients with advanced OG cancer still have a median overall survival of under a year. This review outlines the rationale for the current treatment of OG cancer with chemotherapy and describes both previously conducted and ongoing clinical trials of novel agents in this area. The targets and associated treatments discussed include HER-2, EGFR, VEGF, c-Met, FGFR-2, PI3K, mTOR andIGF-1. To date only two targeted treatments, trastuzumab and ramucirumab, have become part of the treatment paradigm for OG cancer, partly due to difficulties in defining predictive biomarkers in this disease. However, there are a number of promising drugs in the pipeline and this article seeks to describe these and other potential novel approaches including targeting DNA repair deficiencies and the immune system.
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, Down's Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Young
authors.affiliation: Gastrointestinal Unit, Department of Medicine, Royal Marsden Hospital, Down's Road, Sutton, Surrey, SM2 5PT, UK. ian.chau@rmh.nhs.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Chau
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D066246:ErbB Receptors; D007334:Insulin-Like Growth Factor I; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C546842:MTOR protein, human; C512478:EGFR protein, human; C496353:FGFR2 protein, human; C491743:MET protein, human