A next-generation BRAF inhibitor overcomes resistance to BRAF inhibition in patients with BRAF-mutant cancers using pharmacokinetics-informed dose escalation.
Publication Title
Cancer Discov
Document Type
Article
Publication Date
4-30-2024
Keywords
oregon; chiles
Abstract
RAF inhibitors have transformed treatment for BRAF V600-mutant cancer patients, but clinical benefit is limited by adaptive induction of ERK signaling, genetic alterations that induce BRAF V600 dimerization, and poor brain penetration. Next-generation pan-RAF dimer inhibitors are limited by narrow therapeutic index. PF-07799933 (ARRY-440) is a brain-penetrant, selective, pan-mutant BRAF inhibitor. PF-07799933 inhibited signaling in vitro, disrupted endogenous mutant-BRAF
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pharmacy
DOI
10.1158/2159-8290.CD-24-0024
COinS
