Targeted Therapy in Advanced Gastric Cancer: An Updated Review

Despite great efforts over the years, adenocarcinoma of the stomach remains a difficult disease to manage. It is the second leading cause of cancer death and is the fifth most common cancer worldwide. If diagnosed early, surgical resection can offer definitive therapy. However, disease is often advanced or metastatic at the time of diagnosis and chemotherapy becomes the only option. With increased understanding of the molecular pathways that are responsible for tumor development and proliferation, targeted therapies have become an important part of cancer treatment in the setting of advanced or metastatic disease. Trastuzumab is widely used in HER2-positive breast cancer. Similarly, the ToGA trial established its role in gastric cancer that overexpresses HER2 by demonstrating an overall survival benefit in that cohort. Based on these results, HER2 testing should be performed routinely in patients with metastatic gastric cancer in order to identify patients who can benefit from this biologic agent. Ramucirumab also improves survival either as a single agent or when combined with chemotherapy after disease progression using standard first-line therapy. Unfortunately, these favorable responses are not seen with many other targeted agents in gastric cancer. This review aims to outline and summarize currently available knowledge and clinical data for some of the most common signaling targets and their respective therapeutic trials.