Article
KRASG12C-independent feedback activation of wild-type RAS constrains KRASG12C inhibitor efficacy.
Cell reports - 21 Jun 2022
Ryan Meagan B, Coker Oluwadara, Sorokin Alexey, Fella Katerina, Barnes Haley, Wong Edmond, Kanikarla Preeti, Gao Fengqin, Zhang Youyan, Zhou Lian, Kopetz Scott, Corcoran Ryan B
Abstract excerpt
Although KRAS has long been considered undruggable, direct KRASG12C inhibitors have shown promising initial clinical efficacy. However, the majority of patients still fail to respond. Adaptive feedback reactivation of RAS-mitogen-activated protein kinase (MAPK) signaling has been proposed by our group and others as a key mediator of resistance, but the exact mechanism driving reactivation and the therapeutic...
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