Angiogenesis in esophageal and gastric cancer: a paradigm shift in treatment

Esophageal and stomach cancers are leading cause of cancer death worldwide, killing more than 1 million people each year. In unscreened population, patients' symptoms will trigger diagnostic workup. Most patients are diagnosed with advanced stage and their disease is not amenable to surgical resection. The disease is aggressive in nature and mostly even those patients who have early stage disease will eventually succumb to recurrence after definitive therapy. Patients with advanced esophageal and stomach cancers have very limited options for target agents and conventional chemotherapy has remained the standard of care.

Since its discovery, antiangiogenesis continues to be the repeating theme of cancer therapy of the modern era. However, although successful in other tumor types, the data from highly anticipated antiangiogenic agents from both the small molecule tyrosine kinase inhibitors and monoclonal antibodies for esophageal and gastric cancers had been disappointing. Many attribute the lack of survival benefit noted in clinical trials to the failure in identifying target in this patient population.

The most recent clinical studies support that specifically attacking vascular endothelial growth factor receptors remain effective in esophageal and gastric cancers. These pivotal trials may prove to shift the paradigm of current therapy and will likely gain approval for the drug of interest. At the same time, the results generate more questions to understand the disease biology as well as to identify those patients who will benefit the most from such therapy.