title: Clinical impact of tumour biology in the management of gastroesophageal cancer.
abstract: The characterization of oesophageal and gastric cancer into subtypes based on genotype has evolved in the past decade. Insights into the molecular landscapes of gastroesophageal cancer provide a roadmap to assist the development of new drugs and their use in combinations, for patient stratification, and for trials of targeted therapies. Trastuzumab is the only approved treatment for gastroesophageal cancers that overexpress HER2. Acquired resistance usually limits the duration of response to this treatment, although a number of new agents directed against HER2 have the potential to overcome or prolong the time until resistance occurs. Beyond that, anti-VEGFR2 therapy with ramucirumab was the first biological treatment strategy to produce a survival benefit in an unselected population of patients with chemotherapy-refractory gastroesophageal cancer. Large initiatives are starting to address the role of biomarker-driven targeted therapy in the metastatic and in the perioperative setting for patients with this disease. Immunotherapy also holds promise, and our understanding of subsets of gastroesophageal cancer based on patterns of immune response continues to evolve. Efforts are underway to identify more relevant genomic subsets through genomic screening, functional studies, and molecular characterization. Herein, we provide an overview of the key developments in the treatment of gastroesophageal cancer, and discuss potential strategies to further optimize therapy by targeting disease subtypes.
authors.affiliation: University Cancer Center Leipzig, University Medicine Leipzig, Liebigstraße 20 D, 04103 Leipzig, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lordick
authors.affiliation: Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Yelena Y
authors.initials: YY
authors.lastname: Janjigian
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000150:complications; D004938:Esophageal Neoplasms / Q000209:etiology / Q000628:therapy*; D018734:Genes, erbB-2; D020022:Genetic Predisposition to Disease / Q000235:genetics; D023281:Genomics / Q000379:methods; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D020935:MAP Kinase Signaling System / Q000235:genetics; D058990:Molecular Targeted Therapy / Q000379:methods*; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013274:Stomach Neoplasms / Q000209:etiology / Q000628:therapy*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C000588866:KDR protein, human; D020794:Receptor Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2