Molecularly targeted therapies in advanced gastric cancer

Gastric cancer is a prevalent and deadly disease with poor survival of patients with metastatic disease. Although distinct epidemiologic and histologic subtypes of gastric cancer can be identified, the disease is commonly grouped together as a single disease and treated as on entity. However, as molecularly targeted therapies are applied to gastric cancer, this disease heterogeneity has increasingly become clinically relevant. In this review, we summarize the development of agents targeting the human epidermal growth factor receptor (HER) family HER 2 and epidermal growth factor receptor EGFR), vascular endothelial growth factor (VEGF), MET and regulators of cell cycle as they are integrated into therapeutic studies with the goal of improving therapeutic options for this disease. We summarize the rationale for targeting these pathways, in the context of an emerging paradigm of gastric cancer as three unique disease subtypes. The results of the clinical trials evaluating these agents, including completed and ongoing evaluations, are summarized.