Novel targets in esophageal and gastric cancer: beyond antiangiogenesis

Cancers of the stomach, gastroesophageal junction and esophagus are a major cause of cancer-related deaths worldwide. In Western countries, adenocarcinomas of the distal esophagus, gastroesophageal junction and proximal stomach have been increasing in frequency more rapidly than other malignancies. The majority of newly diagnosed patients present with advanced disease and the overall survival remains dismal at approximately 10% at 5 years. Better understanding of tumor biology has led to the development of promising novel therapeutic strategies. There is therefore increasing optimism that some of these approaches will improve the outcomes in these increasingly common cancers. Given the success of antiangiogenesis as a therapeutic strategy in various types of cancer, there are ongoing efforts to investigate the utility of other targeted therapies in the treatment of gastric and esophageal cancers. This review will focus on novel therapeutic targets other than angiogenesis and provide a rationale for the further clinical evaluation of these agents in patients with upper gastrointestinal tract cancers.