Enhanced Antitumor Efficacy of TAS-117 in Combination with Chemotherapy and Targeted Therapies

TAS-117 is a novel, selective small molecule inhibitor of AKT, a key enzyme involved in cell survival and proliferation, often activated in chemoresistant or relapsed cancers. The study aimed to explore the potential of TAS-117 in combination with various chemotherapeutic agents and targeted drugs to enhance antitumor effects.

In vitro assays using human ovarian and gastric cancer cell lines demonstrated that TAS-117 could augment the cytotoxicity of several chemotherapy drugs. In mouse models with subcutaneous tumor xenografts, TAS-117 was administered orally alongside drugs such as carboplatin, irinotecan, S-1, everolimus, and lapatinib, as well as the monoclonal antibody trastuzumab. Treatments were given either orally or via injection, and tumor growth and body weight were monitored.

Results showed that TAS-117 significantly boosted the efficacy of carboplatin and irinotecan in an ovarian cancer model and enhanced the effect of S-1 in a gastric cancer model. Notably, TAS-117 in combination with everolimus induced synergistic growth inhibition and apoptosis in gastric cancer cells, an effect not observed with single-agent treatments. Similarly, TAS-117 displayed synergistic growth inhibition when combined with the HER2 inhibitor lapatinib and trastuzumab, leading to marked antitumor activity in gastric cancer models.

The study concludes that TAS-117, through vertical pathway inhibition and combination with chemotherapeutic and molecular targeted drugs, shows promise as a cancer treatment. These findings support the further clinical investigation of TAS-117 in combination therapies.