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

ABSTRACT:

Background

Most gastrointestinal stromal tumours (GISTs) are driven by KIT proto-oncogene, receptor tyrosine kinase (KIT). Targeted treatment with imatinib has been successful in primary GIST patients. However, resistance and relapse gradually develop due to secondary KIT mutations. Identifying novel therapeutic targets for advanced GIST with KIT mutants is critical.

Methods

Clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 gene editing, immunoblotting, immunoprecipitation and cell-based assays were used to characterise the role of Src homology region 2 domain-containing phosphatase 2 (SHP2) in GIST. Immunoblotting, cell cycle analysis, transcriptome analysis and rescue experiments were performed to investigate the molecular mechanisms underlying SHP2 inhibit

SUBMITTER: He C 

PROVIDER: S-EPMC11843164 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature