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. This article is featured in Selected Articles from This Issue, p. 897.