{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:14:22Z","timestamp":1783318462769,"version":"3.54.6"},"reference-count":50,"publisher":"Open Exploration Publishing","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Explor Target Antitumor Ther"],"accepted":{"date-parts":[[2026,5,17]]},"abstract":"<jats:p xml:lang=\"en\">Gastrointestinal stromal tumours (GISTs) are the clearest solid-tumour model of precision oncology because diagnosis, prognosis, and treatment are strongly shaped by molecular genotype. The discovery of activating mutations in KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor alpha (PDGFRA) transformed management by enabling genotype-directed use of tyrosine kinase inhibitors (TKIs) across localized and advanced disease. This review summarizes how molecular classification informs contemporary GIST care, from diagnostic work-up and risk stratification to neoadjuvant, adjuvant, and metastatic treatment planning. KIT exon 11 mutations generally predict sensitivity to standard-dose imatinib, whereas KIT exon 9 tumours may benefit from dose escalation. PDGFRA D842V confers primary resistance to imatinib but sensitivity to avapritinib, illustrating the clinical value of mutation-specific therapy. We also review KIT\/PDGFRA-wild-type GISTs, including succinate dehydrogenase (SDH)-deficient, neurofibromin 1 (NF1)-associated, B-Raf proto-oncogene (BRAF)-mutant, and neurotrophic tyrosine receptor kinase (NTRK)-rearranged subtypes, where extended molecular testing is increasingly important. Surgery remains central in localized disease, but operative timing, extent of resection, and use of neoadjuvant therapy should be individualized according to tumour site, rupture risk, technical feasibility, and genotype. In advanced disease, sequential use of imatinib, sunitinib, regorafenib, ripretinib, and selected mutation-specific agents reflects evolving resistance biology and the need for ongoing molecular interpretation. Emerging tools such as broader genomic profiling and liquid biopsy may further refine treatment selection. GIST therefore demonstrates that precision oncology is most effective when molecular diagnostics, surgery, systemic therapy, and multidisciplinary decision-making are integrated across the full disease course.<\/jats:p>","DOI":"10.37349\/etat.2026.1002378","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:20:02Z","timestamp":1783315202000},"update-policy":"https:\/\/doi.org\/10.37349\/open_exploration_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Why precision oncology works: lessons from gastrointestinal stromal tumours"],"prefix":"10.37349","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6830-3730","authenticated-orcid":false,"given":"Si Ying Adelina","family":"Ho","sequence":"first","affiliation":[{"name":"Ministry of Health Holdings, Singapore 139691, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwyn Hong Sheng","family":"Tok","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Qi Megan Kimberly","family":"Han","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-3528","authenticated-orcid":false,"given":"Jens","family":"Samol","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tan Tock Seng Hospital, Singapore 308433, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-8142","authenticated-orcid":false,"given":"Vishal G","family":"Shelat","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"21850","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.gtc.2013.01.001","article-title":"Gastrointestinal stromal tumors","volume":"42","author":"Miettinen","year":"2013","journal-title":"Gastroenterol Clin North Am"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Kumar V, Abbas AK, Aster JC, Deyrup AT, editor. 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