Preclinical evidence for synergistic effects of autophagy inhibitor and alpelisib in PI3KCA mutated non-small cell lung cancer: Implications for future clinical trials

e21022 Background: The PI3K pathway is frequently activated in a variety of cancers including non-small cell lung cancer (NSCLC). PI3K mutation is associated with worse response to chemotherapy and consequently decrease the effectiveness of single administration of anticancer drugs. In this study, we checked the therapeutic efficacy of alpelisib either alone or in combination with an autophagy inhibitor for the treatment of NSCLC. Methods: We treated alpelisib and autophagy inhibitors in human NSCLC cell lines and measured the cell viability and protein expression of autophagy indicators, p62 and LC3B. Co-treatment of alpelisib and autophagy inhibitors significantly decrease the cell viability and proliferation compared to alpelisib alone. Based on the results of the combination experiment of alpelisib and autophagy inhibitors, Chloroquine (CQ) was selected for further study. Co-treatment of alpelisib and CQ significantly increase apoptosis and decrease tumor-related protein expression in in vitro and in vivo. Results: Our data demonstrates that alpelisib and autophagy inhibitor have a synergistic efficacy against NSCLC in vitro and in vivo. Conclusions: Based on these results, a Phase 1 clinical trial is currently being planned.