Therapeutic Implications of mTOR Inhibitors in the Treatment of Gastric Cancer

Gastric cancer remains one of the most common types of cancer worldwide, and most patients present with advanced disease. Sixty percent of these patients eventually relapse after curative surgical resection, and combination chemotherapy regimens only provide limited survival benefits. Mammalian target of rapamycin (mTOR) is a new target of cancer therapies. Preclinical data suggest that the suppression of the mTOR pathway inhibits the progression of gastric cancer in vitro and in animal models. In clinical trials, the mTOR inhibitor, everolimus, was well tolerated in phase I/II studies on patients with metastatic gastric cancer. The efficacy of everolimus was promising in a phase II clinical trial, but in a recently published phase III clinical trial everolimus monotherapy do not significantly improve the overall survival of patients with advanced gastric cancer who had been previously treated with one or two lines of systemic chemotherapy. Phosphoinositide 3-kinase/mTOR dual inhibitors have not yet entered early-stage clinical trials in patients with advanced gastric cancer. Further studies are needed to establish the role of mTOR inhibitors for the treatment of gastric cancer.