{"entity":{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","aka":[],"tldr":"GIST is a sarcoma of the gut wall driven almost always by a KIT or PDGFRA mutation. It was the proof that a pill can control a solid tumour: imatinib turned a median survival of about a year into one of eight years or more, and the mutation now dictates which drug to use.","summary":"GIST arises from interstitial cells of Cajal and carries activating KIT mutations (~75%, mostly exon 11, some exon 9) or PDGFRA mutations (~10%, including the imatinib-resistant D842V); the remainder are SDH-deficient (young patients, Carney-Stratakis), NF1-associated, or BRAF/NTRK-driven. Risk after resection is estimated from size, mitotic rate and site (Miettinen/AFIP, modified NIH).\n\nSurgery is the only cure; adjuvant imatinib for three years improves survival in high-risk disease (SSGXVIII), with five years or longer under study. Advanced disease is treated with imatinib (400 mg; 800 mg for exon 9), then sunitinib (2006), regorafenib (2013) and ripretinib (INVICTUS, 2020) in sequence; avapritinib is the drug for PDGFRA D842V (2020). Resistance comes from secondary KIT mutations in the ATP-binding pocket (exon 13/14) or activation loop (exon 17/18) and is heterogeneous across lesions, which is why single next-generation inhibitors have struggled (INTRIGUE: ripretinib not superior to sunitinib overall, but better in ctDNA-defined exon 11 + 17/18 disease, now tested in INSIGHT) and why combinations (bezuclastinib + sunitinib, Peak) and ctDNA-guided selection are the current strategy. SDH-deficient GIST is TKI-insensitive and slow-growing; temozolomide has activity.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Gastrointestinal_stromal_tumor","links":[{"label":"NCCN Guidelines: GIST","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1507"},{"label":"ESMO-EURACAN GIST guideline (2022)","url":"https://doi.org/10.1016/j.annonc.2021.09.005"},{"label":"Life Raft Group (patient organisation)","url":"https://liferaftgroup.org/"}],"tags":["gap-fill","gastrointestinal","sarcoma"],"related":["leiomyosarcoma","desmoid-tumour","inflammatory-myofibroblastic-tumour","dermatofibrosarcoma-protuberans"],"cancers":[],"sections":[],"technologies":["kinase-inhibitors","liquid-biopsy","robotic-surgery","endoscopic-resection"],"targets":["kit","pdgfra","ntrk","braf"],"drugs":["imatinib","sunitinib","regorafenib","ripretinib","avapritinib","temozolomide"],"companies":["novartis","pfizer","bayer","deciphera","sanofi"],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor"],"terms":["oncogene-addiction","resistance","ctdna","gist-risk-stratification","sdh-deficiency"],"trials":["nct07585266","nct05208047","nct07218926","nct07379047","nct03673501","grid","navigator"],"people":[],"bottlenecks":[],"keyPapers":["paper-casali-ann-oncol"],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"GIST affects about 10-15 per million per year (the most common sarcoma); stomach 60%, small bowel 30%; median age ~65.","subtypes":["KIT exon 11-mutant (most common, imatinib-sensitive)","KIT exon 9-mutant (small bowel; imatinib 800 mg)","PDGFRA-mutant (D842V imatinib-resistant → avapritinib)","SDH-deficient (paediatric/young adult, Carney triad)","NF1-associated GIST","BRAF / NTRK-driven (rare)"],"biomarkers":["KIT and PDGFRA mutation status (mandatory before therapy)","Secondary KIT mutations by ctDNA at progression","SDHB immunohistochemistry","Mitotic rate, size, site (risk)","CD117 (KIT) and DOG1 IHC","NF1, BRAF, NTRK in wild-type GIST"],"standardOfCare":[{"setting":"Localised, resectable","approach":"Complete resection without lymphadenectomy; adjuvant imatinib 3 years for high-risk (SSGXVIII); neoadjuvant imatinib to downsize when organ-sparing matters.","refs":["imatinib"],"guideline":{"nccn":"Category 1 (adjuvant imatinib, high risk)","esmoMcbs":"A","version":"NCCN Guidelines: GIST","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1507"}},{"setting":"Advanced, first line","approach":"Imatinib 400 mg (800 mg for KIT exon 9); avapritinib for PDGFRA D842V; continue until progression.","refs":["imatinib","avapritinib"],"guideline":{"nccn":"Category 1","version":"NCCN Guidelines: GIST"}},{"setting":"Advanced, second line","approach":"Sunitinib (or ripretinib for KIT exon 11 + 17/18 secondary mutations per ctDNA, INSIGHT).","refs":["sunitinib","ripretinib","liquid-biopsy"],"guideline":{"nccn":"Category 1 (sunitinib)","version":"NCCN Guidelines: GIST"}},{"setting":"Advanced, third/fourth line","approach":"Regorafenib, then ripretinib (INVICTUS); rechallenge or continue TKI beyond progression; clinical trials (bezuclastinib-sunitinib).","refs":["regorafenib","ripretinib"],"guideline":{"nccn":"Category 1 (regorafenib, ripretinib)","version":"NCCN Guidelines: GIST"}}],"stateOfArt":["Five approved TKIs sequenced by genotype; median survival in advanced GIST is now around 8 years.","ctDNA genotyping of secondary KIT mutations is becoming the way to pick second-line therapy (INSIGHT).","Avapritinib solved the PDGFRA D842V problem with ~90% response.","Combination inhibition (bezuclastinib + sunitinib) aims to cover both ATP-pocket and activation-loop resistance at once."],"history":[{"year":1998,"title":"KIT mutations discovered in GIST (Hirota, Science)","refs":["kit"]},{"year":2000,"title":"Imatinib: dramatic response in a single GIST patient (Joensuu, NEJM 2001)","refs":["imatinib"]},{"year":2002,"title":"Imatinib approved for advanced GIST","refs":["imatinib"]},{"year":2003,"title":"PDGFRA mutations in KIT-wild-type GIST (Heinrich, Science)","refs":["pdgfra"]},{"year":2006,"title":"Sunitinib approved after imatinib failure","refs":["sunitinib"]},{"year":2012,"title":"SSGXVIII: three years of adjuvant imatinib improves overall survival","refs":["imatinib"]},{"year":2013,"title":"Regorafenib approved (GRID)","refs":["regorafenib"]},{"year":2020,"title":"Avapritinib (PDGFRA D842V) and ripretinib (INVICTUS) approved","refs":["avapritinib","ripretinib"]},{"year":2022,"title":"INTRIGUE: ctDNA genotype predicts ripretinib vs sunitinib benefit","refs":["ripretinib","sunitinib"]}],"pipeline":["ripretinib","avapritinib","liquid-biopsy","velzatinib","bezuclastinib","idrx-42","nb003"],"openProblems":["Polyclonal resistance: different lesions carry different secondary KIT mutations.","SDH-deficient and other wild-type GIST have no effective TKI.","Optimal duration of adjuvant imatinib (3 vs 5-6 years).","Long-term imatinib toxicity and adherence."],"parent":"sarcoma"},"route":"/cancers/gist/","neighbours":{"cancer":[{"id":"dermatofibrosarcoma-protuberans","kind":"cancer","name":"Dermatofibrosarcoma protuberans","route":"/cancers/dermatofibrosarcoma-protuberans/"},{"id":"desmoid-tumour","kind":"cancer","name":"Desmoid tumour","route":"/cancers/desmoid-tumour/"},{"id":"gist-imatinib-resistant","kind":"cancer","name":"Imatinib-resistant GIST","route":"/cancers/gist-imatinib-resistant/"},{"id":"inflammatory-myofibroblastic-tumour","kind":"cancer","name":"Inflammatory myofibroblastic tumour (IMT)","route":"/cancers/inflammatory-myofibroblastic-tumour/"},{"id":"gist-kit-exon-11","kind":"cancer","name":"KIT exon 11-mutant GIST","route":"/cancers/gist-kit-exon-11/"},{"id":"leiomyosarcoma","kind":"cancer","name":"Leiomyosarcoma","route":"/cancers/leiomyosarcoma/"},{"id":"gist-pdgfra-d842v","kind":"cancer","name":"PDGFRA D842V-mutant GIST","route":"/cancers/gist-pdgfra-d842v/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"},{"id":"small-bowel","kind":"cancer","name":"Small intestine cancer (small bowel adenocarcinoma)","route":"/cancers/small-bowel/"},{"id":"sdh-deficient-renal-cell-carcinoma","kind":"cancer","name":"Succinate dehydrogenase-deficient renal cell carcinoma","route":"/cancers/sdh-deficient-renal-cell-carcinoma/"},{"id":"systemic-mastocytosis","kind":"cancer","name":"Systemic mastocytosis","route":"/cancers/systemic-mastocytosis/"}],"technology":[{"id":"endoscopic-resection","kind":"technology","name":"Endoscopic resection (EMR / ESD)","route":"/technologies/endoscopic-resection/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"chd2","kind":"target","name":"CHD2","route":"/targets/chd2/"},{"id":"kit","kind":"target","name":"KIT","route":"/targets/kit/"},{"id":"max","kind":"target","name":"MAX","route":"/targets/max/"},{"id":"ntrk","kind":"target","name":"NTRK","route":"/targets/ntrk/"},{"id":"pdgfra","kind":"target","name":"PDGFRA","route":"/targets/pdgfra/"},{"id":"sdha","kind":"target","name":"SDHA","route":"/targets/sdha/"},{"id":"sdhb","kind":"target","name":"SDHB","route":"/targets/sdhb/"},{"id":"sdhc","kind":"target","name":"SDHC","route":"/targets/sdhc/"}],"drug":[{"id":"avapritinib","kind":"drug","name":"Avapritinib","route":"/drugs/avapritinib/"},{"id":"bezuclastinib","kind":"drug","name":"Bezuclastinib","route":"/drugs/bezuclastinib/"},{"id":"idrx-42","kind":"drug","name":"IDRX-42","route":"/drugs/idrx-42/"},{"id":"imatinib","kind":"drug","name":"Imatinib","route":"/drugs/imatinib/"},{"id":"nb003","kind":"drug","name":"NB003","route":"/drugs/nb003/"},{"id":"regorafenib","kind":"drug","name":"Regorafenib","route":"/drugs/regorafenib/"},{"id":"ripretinib","kind":"drug","name":"Ripretinib","route":"/drugs/ripretinib/"},{"id":"sunitinib","kind":"drug","name":"Sunitinib","route":"/drugs/sunitinib/"},{"id":"temozolomide","kind":"drug","name":"Temozolomide","route":"/drugs/temozolomide/"},{"id":"velzatinib","kind":"drug","name":"Velzatinib","route":"/drugs/velzatinib/"}],"company":[{"id":"ab-science","kind":"company","name":"AB Science","route":"/companies/ab-science/"},{"id":"arog-pharmaceuticals","kind":"company","name":"Arog Pharmaceuticals","route":"/companies/arog-pharmaceuticals/"},{"id":"bayer","kind":"company","name":"Bayer","route":"/companies/bayer/"},{"id":"deciphera","kind":"company","name":"Deciphera Pharmaceuticals (Ono)","route":"/companies/deciphera/"},{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"},{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"},{"id":"sanofi","kind":"company","name":"Sanofi","route":"/companies/sanofi/"}],"pathway":[{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"gist-risk-stratification","kind":"term","name":"GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria)","route":"/terms/gist-risk-stratification/"},{"id":"oncogene-addiction","kind":"term","name":"Oncogene addiction","route":"/terms/oncogene-addiction/"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"},{"id":"sdh-deficiency","kind":"term","name":"SDH deficiency (SDHB immunohistochemistry loss)","route":"/terms/sdh-deficiency/"}],"trial":[{"id":"nct05208047","kind":"trial","name":"(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors","route":"/trials/nct05208047/"},{"id":"nct06630234","kind":"trial","name":"A Master Protocol to Evaluate DCC-3009 in Gastrointestinal Stromal Tumor (GIST)","route":"/trials/nct06630234/"},{"id":"nct07218926","kind":"trial","name":"A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy","route":"/trials/nct07218926/"},{"id":"nct06640361","kind":"trial","name":"A Study of Olverembatinib in SDH-deficient GIST.","route":"/trials/nct06640361/"},{"id":"nct03673501","kind":"trial","name":"A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib","route":"/trials/nct03673501/"},{"id":"nct07585266","kind":"trial","name":"A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline)","route":"/trials/nct07585266/"},{"id":"nct07379047","kind":"trial","name":"Efficacy and Safety of NB003 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)","route":"/trials/nct07379047/"},{"id":"grid","kind":"trial","name":"GRID","route":"/trials/grid/"},{"id":"navigator","kind":"trial","name":"NAVIGATOR","route":"/trials/navigator/"}],"paper":[{"id":"paper-casali-ann-oncol","kind":"paper","name":"Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up","route":"/key-papers/paper-casali-ann-oncol/"}],"person":[{"id":"george-demetri","kind":"person","name":"George D. Demetri","route":"/people/george-demetri/"},{"id":"heikki-joensuu","kind":"person","name":"Heikki Joensuu","route":"/people/heikki-joensuu/"},{"id":"michael-heinrich","kind":"person","name":"Michael C. Heinrich","route":"/people/michael-heinrich/"},{"id":"piotr-rutkowski","kind":"person","name":"Piotr Rutkowski","route":"/people/piotr-rutkowski/"},{"id":"sebastian-bauer","kind":"person","name":"Sebastian Bauer","route":"/people/sebastian-bauer/"}],"biomarker":[{"id":"kit-d816v","kind":"biomarker","name":"KIT D816V","route":"/biomarkers/kit-d816v/"},{"id":"pdgfra-exon-18-d842v","kind":"biomarker","name":"PDGFRA exon 18 mutation (D842V)","route":"/biomarkers/pdgfra-exon-18-d842v/"}],"journal":[{"id":"journal-of-gastrointestinal-cancer","kind":"journal","name":"Journal of gastrointestinal cancer","route":"/journals/journal-of-gastrointestinal-cancer/"}]}}