Targeted therapies in metastatic esophageal cancer: Advances over the past decade

Esophageal cancer is one of the most aggressive malignancies of the upper aerodigestive tract. Despite advances in surgical techniques and multi-modality therapies, the 5-year survival rate remains poor (14%). Over the past decade, efforts have been focused on the field of drug development with the advancement of novel molecularly targeted therapeutic agents. These agents target a variety of cancer relevant pathways such as vascular endothelial growth factor (VEGF) or its receptor, the cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and mammalian target of rapamycin (mTOR) pathways. The number of approved targeted agents remains few, with HER-2 inhibitors leading the list for treatment of HER-2 expressing metastatic adenocarcinomas. Novel agents have not yet been widely explored in esophageal cancer. In this review, we will provide a concise and systematic overview of the development of novel targeted therapies currently under investigation for the treatment of metastatic esophageal disease.