Journal
NATURE REVIEWS DISEASE PRIMERS
Volume 7, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41572-021-00254-5
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Funding
- Japanese Ministry of Education, Culture, Sports, Science and Technology [19H03722]
- National Cancer Center Research and Development Fund [31-A-14]
- NetSARC (INCA DGOS)
- LYRICAN (INCA-DGOS-INSERM) [12563]
- Association DAM's
- Eurosarc [FP7-278742]
- Fondation ARC
- Infosarcome
- InterSARC (INCA)
- LabEx DEvweCAN [ANR-10-LABX0061]
- PIA Institut Convergence Francois Rabelais PLAsCAN (PLASCAN) [17-CONV-0002]
- La Ligue de L'Ain contre le Cancer
- La Ligue contre le Cancer
- EURACAN [EC 739521]
- RHU4 DEPGYN [ANR-18-RHUS-0009]
- RREPS (INCA DGOS)
- Grants-in-Aid for Scientific Research [19H03722] Funding Source: KAKEN
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Gastrointestinal stromal tumours (GIST) are rare malignancies with 80% of cases having KIT or PDGFRA activating mutations. Localized GIST can be cured through surgery, while advanced resistant GIST with resistance mutations require treatment with new drugs.
Gastrointestinal stromal tumours (GIST) have an incidence of similar to 1.2 per 10(5) individuals per year in most countries. Around 80% of GIST have varying molecular changes, predominantly mutually exclusive activating KIT or PDGFRA mutations, but other, rare subtypes also exist. Localized GIST are curable, and surgery is their standard treatment. Risk factors for relapse are tumour size, mitotic index, non-gastric site and tumour rupture. Patients with GIST with KIT or PDGFRA mutations sensitive to the tyrosine kinase inhibitor (TKI) imatinib that are at high risk of relapse have improved survival with adjuvant imatinib treatment. In advanced disease, median overall survival has improved from 18 months to >70 months since the introduction of TKIs. The role of surgery in the advanced setting remains unclear. Resistance to TKIs arise mainly from subclonal selection of cells with resistance mutations in KIT or PDGFRA when they are the primary drivers. Advanced resistant GIST respond to second-line sunitinib and third-line regorafenib, as well as to the new broad-spectrum TKI ripretinib. Rare molecular forms of GIST with alterations involving NF1, SDH genes, BRAF or NTRK genes generally show primary resistance to standard TKIs, but some respond to specific inhibitors of the activated genes. Despite major advances, many questions in both advanced and localized disease remain unanswered.
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