Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G. Management of malignant gastrointestinal stromal tumours. Lancet Oncol. 2002;3(11):655–64. https://doi.org/10.1016/s1470-2045(02)00899-9.

Article  CAS  PubMed  Google Scholar 

Nilsson B, Bumming P, Meis-Kindblom JM, Oden A, Dortok A, Gustavsson B, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era–a population-based study in western Sweden. Cancer. 2005;103(4):821–9. https://doi.org/10.1002/cncr.20862.

Article  PubMed  Google Scholar 

Heinrich MC, Rankin C, Blanke CD, Demetri GD, Borden EC, Ryan CW, et al. Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017;3(7):944–52. https://doi.org/10.1001/jamaoncol.2016.6728.

Article  PubMed  PubMed Central  Google Scholar 

von Mehren M, Joensuu H. Gastrointestinal Stromal Tumors. J Clin Oncol. 2018;36(2):136–43. https://doi.org/10.1200/JCO.2017.74.9705.

Article  Google Scholar 

Janeway KA, Kim SY, Lodish M, Nose V, Rustin P, Gaal J, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci U S A. 2011;108(1):314–8. https://doi.org/10.1073/pnas.1009199108.

Article  PubMed  Google Scholar 

Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol. 2004;22(18):3813–25. https://doi.org/10.1200/JCO.2004.05.140.

Article  CAS  PubMed  Google Scholar 

Liu W, Zeng X, Wu X, He J, Gao J, Shuai X, et al. Clinicopathologic study of succinate-dehydrogenase-deficient gastrointestinal stromal tumors: A single-institutional experience in China. Medicine (Baltimore). 2017;96(32):e7668. https://doi.org/10.1097/MD.0000000000007668.

Article  PubMed  Google Scholar 

Pasini B, McWhinney SR, Bei T, Matyakhina L, Stergiopoulos S, Muchow M, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet. 2008;16(1):79–88. https://doi.org/10.1038/sj.ejhg.5201904.

Article  CAS  PubMed  Google Scholar 

Pantaleo MA, Lolli C, Nannini M, Astolfi A, Indio V, Saponara M, et al. Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations. Genet Med. 2015;17(5):391–5. https://doi.org/10.1038/gim.2014.115.

Article  CAS  PubMed  Google Scholar 

Boikos SA, Pappo AS, Killian JK, LaQuaglia MP, Weldon CB, George S, et al. Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic. JAMA Oncol. 2016;2(7):922–8. https://doi.org/10.1001/jamaoncol.2016.0256.

Article  PubMed  PubMed Central  Google Scholar 

Else T, Greenberg S, Fishbein L. Hereditary paraganglioma-pheochromocytoma syndromes. In: Adam MP, Feldman J, Mirzaa GM, et al, editors. GeneReviews®. Seattle: University of Washington; 1993–2025. https://www.ncbi.nlm.nih.gov/books/NBK1548/.

Killian JK, Kim SY, Miettinen M, Smith C, Merino M, Tsokos M, et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov. 2013;3(6):648–57. https://doi.org/10.1158/2159-8290.CD-13-0092.

Article  CAS  PubMed  PubMed Central  Google Scholar 

An J, Rao A, Ko M. TET family dioxygenases and DNA demethylation in stem cells and cancers. Exp Mol Med. 2017;49(4):e323. https://doi.org/10.1038/emm.2017.5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, et al. Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 2012;26(12):1326–38. https://doi.org/10.1101/gad.191056.112.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nannini M, Rizzo A, Indio V, Schipani A, Astolfi A, Pantaleo MA. Targeted therapy in SDH-deficient GIST. Ther Adv Med Oncol. 2021;13:17588359211023278. https://doi.org/10.1177/17588359211023278.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, et al. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell. 2005;7(1):77–85. https://doi.org/10.1016/j.ccr.2004.11.022.

Article  CAS  PubMed  Google Scholar 

Ruas JL, Poellinger L. Hypoxia-dependent activation of HIF into a transcriptional regulator. Semin Cell Dev Biol. 2005;16(4–5):514–22. https://doi.org/10.1016/j.semcdb.2005.04.001.

Article  CAS  PubMed  Google Scholar 

Semenza G. Signal transduction to hypoxia-inducible factor 1. Biochem Pharmacol. 2002;64(5–6):993–8. https://doi.org/10.1016/s0006-2952(02)01168-1.

Article  CAS  PubMed  Google Scholar 

Neppala P, Banerjee S, Fanta PT, Yerba M, Porras KA, Burgoyne AM, et al. Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors. Cancer Metastasis Rev. 2019;38(3):525–35. https://doi.org/10.1007/s10555-019-09818-0.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shaik F, Cuthbert GA, Homer-Vanniasinkam S, Muench SP, Ponnambalam S, Harrison MA. Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy. Biomolecules. 2020;10(12), https://doi.org/10.3390/biom10121673.

Acevedo VD, Ittmann M, Spencer DM. Paths of FGFR-driven tumorigenesis. Cell Cycle. 2009;8(4):580–8. https://doi.org/10.4161/cc.8.4.7657.

Article  CAS  PubMed  Google Scholar 

Smith BD, Kaufman MD, Lu WP, Gupta A, Leary CB, Wise SC, et al. Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. Cancer Cell. 2019;35(5):738–751 e739, https://doi.org/10.1016/j.ccell.2019.04.006.

Dai S, Zhou Z, Chen Z, Xu G, Chen Y. Fibroblast Growth Factor Receptors (FGFRs): Structures and Small Molecule Inhibitors. Cells. 2019;8(6), https://doi.org/10.3390/cells8060614.

Brooks AN, Kilgour E, Smith PD. Molecular pathways: fibroblast growth factor signaling: a new therapeutic opportunity in cancer. Clin Cancer Res. 2012;18(7):1855–62. https://doi.org/10.1158/1078-0432.CCR-11-0699.

Article  CAS  PubMed  Google Scholar 

Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10(2):116–29. https://doi.org/10.1038/nrc2780.

Article  CAS  PubMed  Google Scholar 

Van Galen J. Created in BioRender.2025. https://biorender.com/d15x998. Accessed 17 Jan 2025.

SUTENT® (sunitinib malate) [tablets]. New York, NY: Pfizer; 2021. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021938s039lbledt.pdf. Accessed 15 Nov 2024.

VOTRIENT® (pazopanib) [tablets]. East Hanover, New Jersey: Novartis Pharmaceuticals Corporation; 2024. U.S. Food and Drug Administration website. https://www.novartis.com/us-en/sites/novartis_us/files/votrient.pdf. Accessed 15 Nov 2024.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) Gastrointestinal Stromal Tumors Version 2.2024. NCCN n.d. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1453. Accessed 3 Jan 2025.

Ben-Ami E, Barysauskas CM, von Mehren M, Heinrich MC, Corless CL, Butrynski JE, et al. Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol. 2016;27(9):1794–9. https://doi.org/10.1093/annonc/mdw228.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ganjoo KN, Villalobos VM, Kamaya A, Fisher GA, Butrynski JE, Morgan JA, et al. A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib. Ann Oncol. 2014;25(1):236–40. https://doi.org/10.1093/annonc/mdt484.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Janeway KA, Albritton KH, Van Den Abbeele AD, D’Amato GZ, Pedrazzoli P, Siena S, et al. Sunitinib treatment in pediatric patients with advanced GIST following failure of imatinib. Pediatr Blood Cancer. 2009;52(7):767–71. https://doi.org/10.1002/pbc.21909.

Article  PubMed  Google Scholar 

Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210. https://doi.org/10.1186/s13643-016-0384-4.

Article  PubMed  PubMed Central