Gastrointestinal stromal tumors (GIST): a contemporary review

Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are characterized by marked molecular and clinical heterogeneity. Most GISTs are driven by activating mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA), resulting in constitutive tyrosine kinase signaling. Advances in molecular pathology and targeted therapy have substantially transformed diagnosis, risk stratification, and management.Methods This narrative review summarizes contemporary evidence regarding the molecular biology, pathology, risk stratification, and multidisciplinary management of localized and advanced GIST, with emphasis on genotype-directed therapy and emerging therapeutic strategies.Results Surgical resection remains the cornerstone of treatment for localized GIST. Risk of recurrence is influenced by tumor size, mitotic index, anatomical site, tumor rupture, and molecular subtype. Adjuvant imatinib improves recurrence-free and overall survival in patients with high-risk, imatinib-sensitive disease, with three years of therapy representing the current standard of care. Neoadjuvant imatinib may facilitate tumor downsizing and organ preservation in selected patients with locally advanced disease. In advanced GIST, sequential tyrosine kinase inhibitor (TKI) therapy has significantly improved outcomes. Imatinib remains standard first-line therapy, followed by sunitinib, regorafenib, and ripretinib in resistant disease. Treatment efficacy is strongly influenced by molecular subtype, exemplified by the intrinsic resistance of PDGFRA D842V-mutant tumors to imatinib and the activity of avapritinib in this setting. Wild-type GISTs, including succinate dehydrogenase-deficient and neurofibromatosis type 1-associated subtypes, remain therapeutically challenging due to limited responsiveness to conventional TKIs.Conclusions Management of GIST is increasingly driven by molecular stratification and evolving understanding of resistance biology. Emerging approaches, including next-generation KIT inhibitors, biomarker-guided therapeutic sequencing, circulating tumor DNA analysis, and rational combination strategies, are expected to further refine personalized treatment and improve outcomes for patients with GIST.