Molecular Targeting Therapy and Biomarker for Advanced Gastric Cancer

Abstract

In recent years, various molecular target agents have been investigated for gastric cancer. Main targets are HER family pathway, angiogenesis system and PI3K-Akt-mTOR intracellular signaling system. The anti-HER2 antibody trastuzumab was shown to prolong the survival of patients with HER2-positive advanced gastric cancer, and is approved by the treatment in advanced gastric cancer. On the other hand, the anti-VEGF antibody bevacizumab could not show survival benefit despite certain effect in progression-free survival and response rate. mTOR inhibitor everolimus showed disease control rate of 54.7% in patients with previously treated gastric cancer in a Japanese phase II trial. However, subsequent global phase III trial, GRANITE-1, which compare everolimus with placebo, could not meet its primary endpoint of overall survival. Recent REAL-III trial also could not show survival benefit of EGFR antibody panitumumab. These three negative phase III trials strongly suggest the importance of developing biomarkers to predict the effectiveness of each agent