Gastrointestinal stromal tumour (GIST)
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.
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.
State of the art today
- 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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Five approved TKIs sequenced by genotype; median survival in advanced GIST is now around 8 years.
GIST affects about 10-15 per million per year (the most common sarcoma); stomach 60%, small bowel 30%; median age ~65.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Complete resection without lymphadenectomy; adjuvant imatinib 3 years for high-risk (SSGXVIII); neoadjuvant imatinib to downsize when organ-sparing matters.
Imatinib 400 mg (800 mg for KIT exon 9); avapritinib for PDGFRA D842V; continue until progression.
Sunitinib (or ripretinib for KIT exon 11 + 17/18 secondary mutations per ctDNA, INSIGHT).
Regorafenib, then ripretinib (INVICTUS); rechallenge or continue TKI beyond progression; clinical trials (bezuclastinib-sunitinib).
Subtypes & biomarkers
top- 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)
- 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
Target prevalence in this cancer
| Target / alteration | Prevalence | Measure | Source |
|---|---|---|---|
| PDGFRA | 10% | PDGFRA mutation | doi.org |
How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.
- 1998KIT mutations discovered in GIST (Hirota, Science)
- 2000Imatinib: dramatic response in a single GIST patient (Joensuu, NEJM 2001)
- 2002Imatinib approved for advanced GIST
- 2003PDGFRA mutations in KIT-wild-type GIST (Heinrich, Science)
- 2006Sunitinib approved after imatinib failure
- 2012SSGXVIII: three years of adjuvant imatinib improves overall survival
- 2013Regorafenib approved (GRID)
- 2020Avapritinib (PDGFRA D842V) and ripretinib (INVICTUS) approved
- 2022INTRIGUE: ctDNA genotype predicts ripretinib vs sunitinib benefit
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.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer CenterBaltimore, USNewsweek oncology #10NCI comprehensivevia Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Breast Cancer Research FoundationNew York, USvia Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Cancer Research UK Manchester InstituteManchester, GBvia Liquid biopsy (ctDNA)
- Central Drugs Standard Control OrganizationNew Delhi, INvia Imatinib
- via Liquid biopsy (ctDNA)
- GIMEMARome, ITvia Imatinib
- HealthCare Global EnterprisesBengaluru, INvia Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Institut Jules BordetBrussels, BEvia Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Istituto di Candiolo IRCCS – FPOCandiolo, ITvia Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Lustgarten FoundationWoodbury, NY, USvia Liquid biopsy (ctDNA)
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia Liquid biopsy (ctDNA)
- via Imatinib
- via Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Queen Mary Hospital / University of Hong KongHong Kong, HKvia Liquid biopsy (ctDNA)
- Seoul St. Mary's HospitalSeoul, KRvia Imatinib
- The Francis Crick InstituteLondon, GBvia Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- via Liquid biopsy (ctDNA)
- Zhongshan Hospital, Fudan UniversityShanghai, CNvia Liquid biopsy (ctDNA)
Questions to ask
topQuestions to ask your oncologist about Gastrointestinal stromal tumour
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example KIT and PDGFRA mutation status, Secondary KIT mutations by ctDNA at progression, SDHB immunohistochemistry, Mitotic rate, size, site, CD117and DOG1 IHC), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include KIT exon 11-mutant, KIT exon 9-mutant, PDGFRA-mutant.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Localised, resectable
- For my situation (localised, resectable), which of the standard options do you recommend and why?Why: Guideline options include: Complete resection without lymphadenectomy; adjuvant imatinib 3 years for high-risk (SSGXVIII); neoadjuvant imatinib to downsize when organ-sparing matters.
- Am I a candidate for Imatinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Imatinib 400 mg (800 mg for KIT exon 9); avapritinib for PDGFRA D842V; continue until progression.
- Am I a candidate for Imatinib, Avapritinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, second line
- For my situation (advanced, second line), which of the standard options do you recommend and why?Why: Guideline options include: Sunitinib (or ripretinib for KIT exon 11 + 17/18 secondary mutations per ctDNA, INSIGHT).
- Am I a candidate for Sunitinib, Ripretinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced, third/fourth line
- For my situation (advanced, third/fourth line), which of the standard options do you recommend and why?Why: Guideline options include: Regorafenib, then ripretinib (INVICTUS); rechallenge or continue TKI beyond progression; clinical trials (bezuclastinib-sunitinib).
- Am I a candidate for Regorafenib, Ripretinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Ripretinib, Avapritinib, Liquid biopsy (ctDNA)?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Polyclonal resistance: different lesions carry different secondary KIT mutations”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “SDH-deficient and other wild-type GIST have no effective TKI”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
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3terms
4Latest papers
topQuery for this cancer: (TITLE:"Gastrointestinal stromal tumour" OR ABSTRACT:"Gastrointestinal stromal tumour" OR TITLE:"GIST" OR ABSTRACT:"GIST") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Gastrointestinal stromal tumour (GIST), not a curated reading list.
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