Article
A PP2A molecular glue overcomes RAS/MAPK inhibitor resistance in KRAS-mutant non-small cell lung cancer.
The Journal of clinical investigation - 1 Dec 2025
Raines Brynne, Tseng-Rogenski Stephanie, Dowdican Amanda C, Peris Irene, Hinderman Matthew, Zawacki Kaitlin P, Barrie Kelsey, Hodges Onishi Gabrielle, Dymond Alexander M, Luther Tahra K, Musser Sydney, Karaj Majchrowski Behirda, Brenner J Chad, Ahmed Aqila, Taylor Derek J, O'Connor Caitlin M, Narla Goutham
Abstract excerpt
The effectiveness of RAS/MAPK inhibitors in treating metastatic KRAS-mutant non-small cell lung cancer (NSCLC) is often hindered by the development of resistance driven by disrupted negative feedback mechanisms led by phosphatases like PP2A. PP2A is frequently suppressed in lung cancer to maintain elevated RAS/MAPK activity. Despite its established role in regulating oncogenic signaling, targeting PP2A with...
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