Article
Reporter-based screening identifies RAS-RAF mutations as drivers of resistance to active-state RAS inhibitors in colorectal cancer.
Science signaling - 22 Jul 2025
Aust Oleksandra, Thiel Moritz R T, Blanc Eric, Lüthen Mareen, Hollek Viola, Astaburuaga-García Rosario, Klinger Bertram, Böhning Francisca, Trinks Alexandra, Beule Dieter, Papke Björn, Horst David, Blüthgen Nils, Sers Christine, Der Channing J, Morkel Markus
Abstract excerpt
Therapy-induced acquired resistance limits the clinical effectiveness of mutation-specific KRAS inhibitors in colorectal cancer (CRC). Here, we investigated whether broad-spectrum, active-state RAS inhibitors meet similar limitations. We found that KRAS-mutant CRC cell lines were sensitive to the RAS(ON) multiselective RAS inhibitor RMC-7977, given that treatment resulted in RAS-RAF-MEK-ERK pathway inhibition;...
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