Developing an Effective BET bromodomain inhibitor Drug Combo to Target SCLC

Division Of Basic Sciences - Nci

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Abstract

Through independent low-throughput analysis, we confirmed the findings of the high-throughput analysis. One combination, mTOR inhibitor (mTORi) and BETi, showed superior anti-tumor efficacy in SCLC cell lines. Furthermore, the mTORi and BETi combination demonstrate superior tumor control and tolerability in several SCLC PDX models. Mechanistically, BETi induces apoptosis but its anti-tumor effect is counteracted by a concomitant transcriptome change that promotes cell survival. mTORi effectively blocks this survival cascade and enhances BETi-induced apoptosis in SCLC.