Co-targeting KRAS G12C and EGFR reduces both mutant and wild-type RAS-GTP

Thomas McFall; Michael Trogdon; Anita C Guizar; John F Langenheim; Laura Sisk-Hackworth; Edward C Stites

doi:10.1038/s41698-022-00329-w

Co-targeting KRAS G12C and EGFR reduces both mutant and wild-type RAS-GTP

NPJ Precis Oncol. 2022 Nov 23;6(1):86. doi: 10.1038/s41698-022-00329-w.

Authors

Thomas McFall¹, Michael Trogdon², Anita C Guizar³, John F Langenheim⁴, Laura Sisk-Hackworth², Edward C Stites^{5

6}

Affiliations

¹ Department of Biochemistry and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. tmcfall@mcw.edu.
² Integrative Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
³ Department of Biochemistry and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
⁴ Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
⁵ Integrative Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA. edward.stites@yale.edu.
⁶ Department of Laboratory Medicine, Yale University, New Haven, CT, 06520, USA. edward.stites@yale.edu.

Abstract

The combination of KRAS G12C inhibitors with EGFR inhibitors has reproducibly been shown to be beneficial. Here, we identify another benefit of this combination: it effectively inhibits both wild-type and mutant RAS. We believe that targeting both mutant and wild-type RAS helps explain why this combination of inhibitors is effective.

Abstract

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