Key Points
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Oesophageal and gastric cancers are aggressive tumours that result in more than 1 million deaths annually worldwide
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Oesophageal and gastric cancers harbour a high number of genetic and molecular alterations, some of which contribute to an aggressiveness phenotype resulting in early development of drug resistance
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A new molecular classification of gastric cancer into four subtypes on the basis of genotypic, epigenetic and proteomic characteristics has been developed
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HER2-targeting with trastuzumab remains an important strategy in patients with HER2-positive, advanced-stage gastric cancer; however, novel anti-HER2 targeted drugs are being explored in the advanced-stage and perioperative treatment settings
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Antiangiogenic treatment with ramucirumab has proved effective in a biologically unselected patient population with disease progression after first-line therapy
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Treatments that target cancer stemness and immune-based therapies are two evolving concepts in the management of advanced-stage 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.
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F.L. has lectured and chaired sponsored symposia for Amgen, Celgene, Eli Lilly, Elsevier, Roche and Taiho. He has received support for participation in scientific congresses from Amgen, Bayer, Eli Lilly, Merck-Serono, Roche and Taiho. He receives research support from Fresenius Biotech, GSK and Merck-Serono. He has also served on advisory boards for BMS, Eli Lilly, Nordic, Roche and Taiho. Y.J. has received research funding from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, Genentech and Merck. She has also served on advisory boards for Eli Lilly and Pfizer.
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Lordick, F., Janjigian, Y. Clinical impact of tumour biology in the management of gastroesophageal cancer. Nat Rev Clin Oncol 13, 348–360 (2016). https://doi.org/10.1038/nrclinonc.2016.15
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DOI: https://doi.org/10.1038/nrclinonc.2016.15
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