{"entity":{"id":"gist-kit-exon-11","kind":"cancer","name":"KIT exon 11-mutant GIST","aka":["Imatinib-sensitive GIST","KIT-mutant gastrointestinal stromal tumour","Classic GIST"],"tldr":"Most GISTs are driven by a mutation in exon 11 of the KIT gene, which keeps the KIT growth receptor switched on. Imatinib blocks it: given for three years after surgery in higher-risk tumours it prevents relapse and extends life, and in metastatic disease it controls the tumour for years before resistance develops.","summary":"Gastrointestinal stromal tumours arise from the interstitial cells of Cajal in the gut wall, and in 1998 Hirota showed that most carry activating mutations of KIT. Exon 11 mutations, which affect the juxtamembrane domain that normally holds the receptor inactive, account for around two thirds of all GISTs, occur at every site, and are the most sensitive to imatinib at 400 mg daily. Deletions involving codons 557 and 558 carry a worse prognosis than substitutions. Mutation testing is required before treatment because exon 9, PDGFRA D842V and wild-type tumours behave differently, and risk of relapse after surgery is estimated from size, mitotic count and site using the Miettinen or modified NIH criteria.\n\nSurgery removes localised tumours with clear margins and without lymph node dissection, since GIST rarely spreads to nodes. Adjuvant imatinib for one year improved recurrence-free survival in ACOSOG Z9001 (2009), and the Scandinavian SSG XVIII trial (JAMA 2012) showed that three years beat one in high-risk tumours, with five-year overall survival of 92 percent against 82 percent; three years is standard for high-risk disease, and trials of five years are ongoing. Neoadjuvant imatinib shrinks large or awkwardly placed tumours, at the rectum or gastro-oesophageal junction, to allow organ-sparing surgery.\n\nIn metastatic disease imatinib controls the tumour for a median of around two years before secondary mutations, in the ATP-binding pocket (exons 13 and 14) or activation loop (exons 17 and 18), cause resistance; the drug is continued indefinitely because stopping it leads to rapid progression. Response is judged on CT with Choi criteria, since tumours may become cystic without shrinking. On progression, dose escalation to 800 mg, then sunitinib, regorafenib and ripretinib follow, and circulating tumour DNA is increasingly used to identify the secondary mutation and choose between them.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Gastrointestinal_stromal_tumor","links":[{"label":"SSG XVIII (JAMA 2012)","url":"https://pubmed.ncbi.nlm.nih.gov/22453568/"},{"label":"ACOSOG Z9001 (Lancet 2009)","url":"https://pubmed.ncbi.nlm.nih.gov/19303137/"},{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastrointestinal_stromal_tumor"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"About two thirds of gastrointestinal stromal tumours carry a mutation in exon 11 of KIT, the juxtamembrane domain; this is the imatinib-sensitive majority in whom the drug turned a lethal sarcoma into a chronic disease.","subtypes":["KIT exon 11 deletion (codons 557-558; higher risk)","KIT exon 11 substitution or duplication (lower risk)","Localised KIT exon 11-mutant GIST, high risk (three years of adjuvant imatinib)","Metastatic KIT exon 11-mutant GIST on imatinib","Gastric versus small bowel KIT-mutant GIST"],"biomarkers":["KIT exon 11 mutation type (deletion versus substitution)","Mitotic count, size and site (Miettinen risk)","KIT (CD117) and DOG1 immunohistochemistry","Secondary KIT mutations on progression (tissue or circulating tumour DNA)","Imatinib plasma level in poor responders"],"standardOfCare":[{"setting":"Localised, resectable","approach":"Complete surgical resection without lymphadenectomy; laparoscopic for smaller gastric tumours; neoadjuvant imatinib for large or poorly placed tumours.","refs":["imatinib","robotic-surgery","kit"]},{"setting":"After resection, high risk","approach":"Three years of adjuvant imatinib 400 mg (SSG XVIII); trials of longer courses.","refs":["imatinib","kit"]},{"setting":"Metastatic, first line","approach":"Imatinib 400 mg continued until progression, with CT response assessment by Choi criteria.","refs":["imatinib","ct","kit"]},{"setting":"Progression on imatinib","approach":"Dose escalation to 800 mg, then sunitinib, regorafenib and ripretinib, ideally guided by the secondary mutation on circulating tumour DNA.","refs":["imatinib","sunitinib","regorafenib","ripretinib","liquid-biopsy","ctdna"]}],"stateOfArt":["Imatinib in KIT-mutant GIST was the first targeted therapy for a solid tumour defined by its driver mutation and remains the model for the field.","Three years of adjuvant imatinib is one of the few adjuvant targeted therapies proven to extend overall survival.","Genotype now dictates dose and drug sequence, with circulating tumour DNA replacing repeat biopsy."],"history":[{"year":1998,"title":"Hirota identifies gain-of-function KIT mutations in GIST","refs":["kit"]},{"year":2001,"title":"First GIST patient treated with imatinib responds (Joensuu)","refs":["imatinib"]},{"year":2002,"title":"B2222 phase 2 and FDA approval of imatinib for metastatic GIST","refs":["imatinib"]},{"year":2009,"title":"ACOSOG Z9001: one year of adjuvant imatinib reduces recurrence","refs":["imatinib"]},{"year":2012,"title":"SSG XVIII: three years of adjuvant imatinib extends overall survival","refs":["imatinib"]}],"pipeline":["idrx-42","nb003","bezuclastinib","liquid-biopsy","insight-gist"],"openProblems":["Whether adjuvant imatinib should continue for five years or longer.","Resistance through secondary KIT mutations in nearly every metastatic patient.","Tumours that recur after stopping adjuvant therapy despite years of control."],"parent":"gist"},"route":"/cancers/gist-kit-exon-11/","neighbours":{"target":[{"id":"kit","kind":"target","name":"KIT","route":"/targets/kit/"}],"drug":[{"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/"}],"technology":[{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"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/"}],"trial":[{"id":"insight-gist","kind":"trial","name":"INSIGHT","route":"/trials/insight-gist/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"}],"cancer":[{"id":"gist","kind":"cancer","name":"Gastrointestinal stromal tumour (GIST)","route":"/cancers/gist/"}]}}