Clinical impact of tumour biology in the management of gastroesophageal cancer

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.