Update on metastatic gastric and esophageal cancers.

Cancers of the stomach and esophagus are among the most challenging cancers of the GI tract to treat, associated with poor median survivals for metastatic disease and significant, sometimes prolonged, deteriorations in patient performance status as the diseases progress. However, in the past decade, we have begun to better understand disease biology and carcinogenesis, leading to the identification of subtypes of these diseases. There is also an increasing awareness of the global heterogeneity of disease and its impact on drug development. Our improved understanding of the molecular underpinnings of gastric and esophageal cancers has been accompanied with the development of novel therapeutic strategies. Recent actively investigated targets in this disease include human epidermal growth factor receptor 2, angiogenesis, MET, and immune checkpoint inhibition, with approvals of two new targeted agents, trastuzumab and ramucirumab. Improvements in our ability to deliver cytotoxic therapy, which is better tolerated and allows patients an opportunity to benefit from second- and more advanced lines of therapy, have also been observed. In this review, the current state-of-the-art management of advanced and metastatic gastric and esophageal adenocarcinomas, specifically highlighting the development of targeted therapies in these diseases, is described.