HER2/neu as target in gastric adenocarcinoma

Gastric adenocarcinoma (GAC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer-related death. The modest activity and substantial toxicity of cytotoxic chemotherapy has raised the question, does palliative systemic therapy with available agents have clinical utility? In the setting of metastatic disease, many active chemotherapy agents can produce meaningful response alone or in combination with other agents, but the duration of response is often limited. Recent additions to the armamentarium include trastuzumab and ramucirumab, which have shown some survival advantage when added to cytotoxic(s). The HER2 proto-oncogene is the gene encoding the human EGF receptor 2. HER2 amplification or protein overexpression [found in 20% of gastric cancer (GC)] is clearly associated with accelerated cell growth and proliferation and the response to the monoclonal anti-HER2 antibody, trastuzumab. HER2 was more likely to be positive in patients with esophagogastric junction (EGJ) tumors than in more distal tumors (33% versus 20%); patients with diffuse GC were much less likely to have an HER2-positive (6%) tumor (1).