Targeting AKT protein kinase in gastric cancer.

Abstract

Gastric cancer is a highly lethal malignancy with more than 700,000 deaths every year worldwide. Despite significant improvements in our understanding of disease biology, the 5-year survival rates remain low. With the exception of trastuzumab, targeted agents have failed to add any meaningful benefit for this patient population, despite promising pre-clinical data. Protein kinase B (AKT) is essential for cell growth, proliferation, and survival. Aberrant activation of AKT is one of the most common molecular findings in human malignancies including gastric cancer, and it is believed to play an important role in cancer cell survival and chemotherapy resistance. Combining phosphatidylinositol 3-kinase (PI3K)/AKT pathway inhibitors with chemotherapy has successfully attenuated chemotherapeutic resistance in gastric cancer cell lines. Drugs designed to specifically target AKT are now being developed for clinical use. In this article, we will review the current knowledge on AKT signaling in the pathogenesis of gastric cancer and the evolving therapeutic implications of targeting this pathway.