For high-risk GIST, KIT/PDGFRA inhibitors such as imatinib, sunitinib, regorafenib, and ripretinib could be administered as neoadjuvant therapy to reduce tumor size and stage, followed by surgery and p53-targeted adjuvant therapy to eliminate residual cancer cells and lower recurrence risk. This evidence concerns the gene KIT and gastrointestinal stromal tumor.