# Gastrointestinal stromal tumour (GIST)

Source: https://onco.cc/cancers/gist/  
OnCo record `gist` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

Surgery 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Tags: gap-fill; gastrointestinal; sarcoma
- 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

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/gist/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/gist/#overview [3 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/gist/#what-it-is [9 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/gist/#finding-it [6 biomarkers, 1 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/gist/#treating-it [4 settings, 2 regimens, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/gist/#evidence [9 trials, 1 key paper, 9 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/gist/#science [12 targets, 3 pathways, 5 preclinical models]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/gist/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/gist/#living-with-it [17 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/gist/coming/ [10 medicines, 9 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/gist/data/ [67 connected records]

## Standard of care

- Localised, resectable: Complete resection without lymphadenectomy; adjuvant imatinib 3 years for high-risk (SSGXVIII); neoadjuvant imatinib to downsize when organ-sparing matters. ([Imatinib](https://onco.cc/drugs/imatinib/))
- Advanced, first line: Imatinib 400 mg (800 mg for KIT exon 9); avapritinib for PDGFRA D842V; continue until progression. ([Imatinib](https://onco.cc/drugs/imatinib/), [Avapritinib](https://onco.cc/drugs/avapritinib/))
- Advanced, second line: Sunitinib (or ripretinib for KIT exon 11 + 17/18 secondary mutations per ctDNA, INSIGHT). ([Sunitinib](https://onco.cc/drugs/sunitinib/), [Ripretinib](https://onco.cc/drugs/ripretinib/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/))
- Advanced, third/fourth line: Regorafenib, then ripretinib (INVICTUS); rechallenge or continue TKI beyond progression; clinical trials (bezuclastinib-sunitinib). ([Regorafenib](https://onco.cc/drugs/regorafenib/), [Ripretinib](https://onco.cc/drugs/ripretinib/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Gastrointestinal_stromal_tumor
- NCCN Guidelines: GIST: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1507
- ESMO-EURACAN GIST guideline (2022): https://doi.org/10.1016/j.annonc.2021.09.005
- Life Raft Group (patient organisation): https://liferaftgroup.org/

## Connected records

- cancers: [Dermatofibrosarcoma protuberans](https://onco.cc/cancers/dermatofibrosarcoma-protuberans/), [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/), [Imatinib-resistant GIST](https://onco.cc/cancers/gist-imatinib-resistant/), [Inflammatory myofibroblastic tumour (IMT)](https://onco.cc/cancers/inflammatory-myofibroblastic-tumour/), [KIT exon 11-mutant GIST](https://onco.cc/cancers/gist-kit-exon-11/), [Leiomyosarcoma](https://onco.cc/cancers/leiomyosarcoma/), [PDGFRA D842V-mutant GIST](https://onco.cc/cancers/gist-pdgfra-d842v/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/), [Small intestine cancer (small bowel adenocarcinoma)](https://onco.cc/cancers/small-bowel/), [Succinate dehydrogenase-deficient renal cell carcinoma](https://onco.cc/cancers/sdh-deficient-renal-cell-carcinoma/), [Systemic mastocytosis](https://onco.cc/cancers/systemic-mastocytosis/)
- technologies: [Endoscopic resection (EMR / ESD)](https://onco.cc/technologies/endoscopic-resection/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Robotic & minimally invasive surgery](https://onco.cc/technologies/robotic-surgery/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/), [CHD2](https://onco.cc/targets/chd2/), [KIT](https://onco.cc/targets/kit/), [MAX](https://onco.cc/targets/max/), [NTRK](https://onco.cc/targets/ntrk/), [PDGFRA](https://onco.cc/targets/pdgfra/), [SDHA](https://onco.cc/targets/sdha/), [SDHB](https://onco.cc/targets/sdhb/), [SDHC](https://onco.cc/targets/sdhc/)
- drugs: [Avapritinib](https://onco.cc/drugs/avapritinib/), [Bezuclastinib](https://onco.cc/drugs/bezuclastinib/), [IDRX-42](https://onco.cc/drugs/idrx-42/), [Imatinib](https://onco.cc/drugs/imatinib/), [NB003](https://onco.cc/drugs/nb003/), [Regorafenib](https://onco.cc/drugs/regorafenib/), [Ripretinib](https://onco.cc/drugs/ripretinib/), [Sunitinib](https://onco.cc/drugs/sunitinib/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Velzatinib](https://onco.cc/drugs/velzatinib/)
- companies: [AB Science](https://onco.cc/companies/ab-science/), [Arog Pharmaceuticals](https://onco.cc/companies/arog-pharmaceuticals/), [Bayer](https://onco.cc/companies/bayer/), [Deciphera Pharmaceuticals (Ono)](https://onco.cc/companies/deciphera/), [Novartis](https://onco.cc/companies/novartis/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/), [Sanofi](https://onco.cc/companies/sanofi/)
- pathways: [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/), [GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria)](https://onco.cc/terms/gist-risk-stratification/), [Oncogene addiction](https://onco.cc/terms/oncogene-addiction/), [Rare cancers](https://onco.cc/terms/rare-cancers/), [SDH deficiency (SDHB immunohistochemistry loss)](https://onco.cc/terms/sdh-deficiency/)
- trials: [(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors](https://onco.cc/trials/nct05208047/), [A Master Protocol to Evaluate DCC-3009 in Gastrointestinal Stromal Tumor (GIST)](https://onco.cc/trials/nct06630234/), [A Study of IDRX-42 (GSK6042981) Versus (vs) Sunitinib in Participants With Gastrointestinal Stromal Tumors After Imatinib Therapy](https://onco.cc/trials/nct07218926/), [A Study of Olverembatinib in SDH-deficient GIST.](https://onco.cc/trials/nct06640361/), [A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib](https://onco.cc/trials/nct03673501/), [A Study to Investigate Velzatinib Compared With Imatinib in Adult Participants With Previously Untreated Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (StrateGIST Frontline)](https://onco.cc/trials/nct07585266/), [Efficacy and Safety of NB003 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)](https://onco.cc/trials/nct07379047/), [GRID](https://onco.cc/trials/grid/), [NAVIGATOR](https://onco.cc/trials/navigator/)
- key papers: [Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-casali-ann-oncol/)
- people: [George D. Demetri](https://onco.cc/people/george-demetri/), [Heikki Joensuu](https://onco.cc/people/heikki-joensuu/), [Michael C. Heinrich](https://onco.cc/people/michael-heinrich/), [Piotr Rutkowski](https://onco.cc/people/piotr-rutkowski/), [Sebastian Bauer](https://onco.cc/people/sebastian-bauer/)
- biomarkers: [KIT D816V](https://onco.cc/biomarkers/kit-d816v/), [PDGFRA exon 18 mutation (D842V)](https://onco.cc/biomarkers/pdgfra-exon-18-d842v/)
- journals: [Journal of gastrointestinal cancer](https://onco.cc/journals/journal-of-gastrointestinal-cancer/)

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JSON: https://onco.cc/api/v1/entities/gist.json