SHP2 inhibition and adjuvant therapy synergistically target KIT-mutant GISTs via ERK1/2-regulated GSK3β/cyclin D1 pathway

Abstract

	•SHP2 plays a pivotal role as a signal transducer in the MAPK/ERK signaling pathway.
	•SHP2 controls the cell cycle via the GSK3β/cyclin D1/Rb pathway in oncogenic KIT-driven GIST.
	•Inhibition of SHP2 synergizes with adjuvant therapy drugs in inhibiting KIT-driven GIST with primary and secondary mutations both in vitro and in vivo.

Keywords

drug resistance / GIST / imatinib / KIT / SHP2

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.