{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:58:15Z","timestamp":1793678295138,"version":"4.5.1"},"reference-count":91,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am Soc Clin Oncol Educ Book"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>\n            GI stromal tumors (GISTs) are mesenchymal neoplasms with variable natural histories, originating in the GI tract, most commonly in the stomach. They are frequently characterized by\n            <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n            or\n            <jats:italic toggle=\"yes\">platelet-derived growth factor receptor alpha<\/jats:italic>\n            (\n            <jats:italic toggle=\"yes\">PDGFRA<\/jats:italic>\n            ) oncogenic mutations. Surgical resection remains the cornerstone treatment for localized GISTs. Clinical trials have demonstrated the benefits of adjuvant imatinib in patients selected on the basis of recurrence risk and gene mutations, although the optimal duration of therapy is yet to be established. Some data suggest that longer durations of adjuvant imatinib (&gt;3 years) may provide additional benefit, which is being investigated in ongoing trials. Management of imatinib-related adverse effects is essential during treatment, and longitudinal abdominal imaging is mandatory both during and after adjuvant therapy. Once GISTs are more advanced and unresectable, KIT- and PDGFRA-directed tyrosine kinase inhibitors (TKIs) become the key treatment in most patients with\n            <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n            mutation. Several TKIs have regulatory approval for advanced GISTs, but in most patients, resistance to TKIs eventually emerges, mainly from secondary resistance mutations in\n            <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n            . Each TKI has different coverage of oncogenic\n            <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n            mutations, suggested by preclinical and clinical findings, which has given rationale to an ongoing clinical trial that includes molecular selection as eligibility criteria. Furthermore, novel treatment approaches, from TKI combinations to an antibody-drug conjugate, are being investigated. Despite the significant advance in managing GISTs with\n            <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n            mutations, those without\n            <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n            or\n            <jats:italic toggle=\"yes\">PDGFRA<\/jats:italic>\n            mutation, which consists of 10%-15% of patients with GIST, can be a clinical challenge in the advanced setting. These non-\n            <jats:italic toggle=\"yes\">KIT\/PDGFRA<\/jats:italic>\n            GISTs could be driven by genomic or epigenomic alterations in\n            <jats:italic toggle=\"yes\">SDHx<\/jats:italic>\n            ,\n            <jats:italic toggle=\"yes\">NF1<\/jats:italic>\n            mutations, and other genomic alterations. Non-\n            <jats:italic toggle=\"yes\">KIT\/PDGFRA<\/jats:italic>\n            GISTs are less responsive to currently available TKIs than GISTs driven by\n            <jats:italic toggle=\"yes\">KIT\/PDGFRA<\/jats:italic>\n            mutations, and each subset of non-\n            <jats:italic toggle=\"yes\">KIT\/PDGFRA<\/jats:italic>\n            GIST has distinctive biology and clinical features. Therefore, individualized, multidisciplinary, biology-based management and consideration for clinical trial enrollment are critical for non-\n            <jats:italic toggle=\"yes\">KIT\/PDGRFA<\/jats:italic>\n            GISTs.\n          <\/jats:p>","DOI":"10.1200\/edbk-25-473224","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T19:59:07Z","timestamp":1747771147000},"source":"Crossref","is-referenced-by-count":5,"title":["Navigating Ongoing Challenges in GI Stromal Tumors"],"prefix":"10.1200","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-2507","authenticated-orcid":true,"given":"Heikki","family":"Joensuu","sequence":"first","affiliation":[{"name":"Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, 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