A novel mTORC1/2 inhibitor (MTI-31) inhibits tumor growth, epithelial-mesenchymal transition, metastases and improves cancer immunity in preclinical lung cancer models

Purpose: We aimed to investigate efficacy and mechanism of MTI-31 (LXI-15029), a novel mTORC1/mTORC2 inhibitor currently in human trial (NCT03125746), in non-small cell lung cancer (NSCLC) models of multiple driver mutations and tyrosine kinase inhibitor (TKI)-resistance. Experimental design: Gene depletion, inhibitor treatment, immunological, flow cytometry, cellular and animal studies were performed to determine in vitro and in vivo efficacy in NSCLC models of driver mutations and elucidate roles by mTOR-complexes in regulating migration, epithelial-mesenchymal transition (EMT), metastasis, intracranial tumor growth and immune-escape. Results: MTI-31 potently inhibited cell proliferation (IC 50