MTOR Inhibitor MLN0128 has Antitumor Efficacy in Cell Lines With Intrinsic and Acquired Rapamycin-Resistance.

Abstract

The mammalian target of rapamycin (mTOR) pathway plays a central role in cancer biology. mTOR forms two multiprotein complexes, mTOR complex 1 and 2 (mTORC1 and mTORC2). Rapamycin and analogues are allosteric mTOR inhibitors that predominantly inhibit mTORC1. Rapamycin analogues have been FDA approved for several cancer types and are in clinical trials for treatment of many others. MLN0128 is a mTOR kinase inhibitor, that inhibit s both mTORC1 and mTORC2. We hypothesized that MLN0128 may have antitumor efficacy in cancer cell lines with intrinsic or acquired rapamycin-resistance.