Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers.
Jingjing JiangLingyan JiangBenjamin J MaldonatoYingyun WangMatthew HolderfieldIda AronchikIan P WintersZeena SalmanCristina BlajMarie MenardJens BrodbeckZhe ChenXing WeiMichael J RosenYevgeniy GindinBianca J LeeJames W EvansStephanie ChangZhican WangKyle J SeamonDylan ParsonsJames CreggAbby MarquezAidan C A TomlinsonJason K YanoJohn E KnoxElsa QuintanaAndrew J AguirreKathryn C ArbourAbby ReedW Clay GustafsonAdrian L GillElena S KoltunDavid WildesJacqueline A M SmithZhengping WangMallika SinghPublished in: Cancer discovery (2024)
The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors.