KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST

• DOI: 10.1186/s12964-023-01411-x
• Publication Date: 2024-02-27T11:02:33Z
• Authors: Shishan Zhou; Omar Abdihamid; Fengbo Tan; Haiyan Zhou; Heli Liu; Zhi Li; Sheng Xiao; Bin Li
• Keywords: Proto-Oncogene Proteins c-kit; Stromal tumor

Abstract Gastrointestinal stromal tumor (GIST) is the most common sarcoma located in gastrointestinal tract and derived from interstitial cell of Cajal (ICC) lineage. Both ICC GIST cells highly rely on KIT signal pathway. Clinically, about 80-90% treatment-naive patients harbor primary mutations, special KIT-targeted TKI, imatinib (IM) showing dramatic efficacy but resistance invariably occur, 90% them was due to second mutations emerging within gene. Although there are multiple variants mutant which did not show complete uniform biologic characteristics, have high expression level. Notably, level gene correlated its amplification. Recently, accumulating evidences strongly indicated that coding, epigenetic regulation, pre- or post- protein translation mutants were quite different wild type (WT) KIT. In this review, we elucidate mechanism update underlying gene, exclusively regulated GIST, providing a promising yet evidence-based therapeutic landscape possible target for conquer IM resistance.