Article
A Next-Generation BRAF Inhibitor Overcomes Resistance to BRAF Inhibition in Patients with BRAF-Mutant Cancers Using Pharmacokinetics-Informed Dose Escalation.
Cancer discovery - 4 Sept 2024
Yaeger Rona, McKean Meredith A, Haq Rizwan, Beck J Thaddeus, Taylor Matthew H, Cohen Jonathan E, Bowles Daniel W, Gadgeel Shirish M, Mihalcioiu Catalin, Papadopoulos Kyriakos P, Diamond Eli L, Sturtz Keren B, Feng Gang, Drescher Stefanie K, Reddy Micaela B, Sengupta Bhaswati, Maity Arnab K, Brown Suzy A, Singh Anurag, Brown Eric N, Baer Brian R, Wong Jim, Mou Tung-Chung, Wu Wen-I, Kahn Dean R, Gadal Sunyana, Rosen Neal, Gaudino John J, Lee Patrice A, Hartley Dylan P, Rothenberg S Michael
Abstract excerpt
RAF inhibitors have transformed treatment for patients with BRAFV600-mutant cancers, but clinical benefit is limited by adaptive induction of ERK signaling, genetic alterations that induce BRAFV600 dimerization, and poor brain penetration. Next-generation pan-RAF dimer inhibitors are limited by a narrow therapeutic index. PF-07799933 (ARRY-440) is a brain-penetrant, selective, pan-mutant BRAF inhibitor....
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