The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor
Abstract
:1. Introduction
2. FGF/FGFR Family
3. FGF/FGFR Events in GIST
4. FGFR Mutations and Gene Fusions
5. FGFR Ligand Overexpression
6. FGFR Events and Imatinib Resistance in KIT/PDGFRA Mutant GIST
7. Clinical Perspectives
8. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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n Cases | FGF/FGFR Alteration | Methodology | GIST Classification | |
---|---|---|---|---|
Shi et al., 2016 [21] | 1 | FGFR1 K656E | Target gene panel | quadruple WT GIST |
2 | FGFR1-TACC1 | Target gene panel | quadruple WT GIST | |
1 | FGFR1-HOOK3 | Target gene panel | quadruple WT GIST | |
Pantaleo et al., 2017 [22] | 1 | FGFR1 N546K | Whole exome seq | quadruple WT GIST |
Urbini et al., 2019 [25] | 6 | FGF4 duplication and overexpression | SNP-array, RNA sequencing | quadruple WT GIST |
Flavahan et al., 2019 [26] | 19 * | FGF insulator methylation and FGF3/FGF4 overexpression | CTCF ChIP and bisulfite seq, HiC and 4C, RNA sequencing | SDH-deficient GIST |
Drug | Target | References in GIST |
---|---|---|
Multi-kinase inhibitors | ||
Regorafenib | FGFR1, VEGFR1,2.3 TIE2, KIT, RET, RAF-1, BRAF, and BRAF V600E, PDGFRβ | [3,56,57] |
Dovitinib | FGFR1/3, VEGFR1/2/3, PDGFRβ, KIT, RET | [58,59] |
Masitinib | FGFR3, PDGFRα/β, Lck, FAK | [60,61,62] |
Ponatinib | FGFR1/2/3/4, Abl, PDGFRα/β, RET, KIT, CSF1R, FLT3, VEGFR1/2/3 | [63] |
Pazopanib | FGFR1, VEGFR1/2/3, PDGFRβ, KIT | [64,65] |
Lenvatinib | FGFR1/2/3, VEGFR1/2/3, RET, KIT | [66] |
Nindetanib | FGFR1, VEGFR2/3, PDGFRα | - |
Lucitanib | FGFR1, VEGFR1/2, PDGFRα/β,Src | - |
FGFR inhibitors | ||
Erdafitinib | FGFR1/2/3/4 | - |
Futibatinib | FGFR1/2/3/4 | - |
LY2874455 | FGFR1/2/3/4 | - |
Rogaratinib | FGFR1/2/3/4 | - |
PRN1371 | FGFR1/2/3/4 | - |
Infigratinib | FGFR1/2/3 | [67] |
Pemigatinib | FGFR1/2/3 | - |
Debio 1347 | FGFR1/2/3 | [68] |
AZD4547 | FGFR1/2/3 | - |
Roblitinib | FGFR4 | - |
H3B-6527 | FGFR4 | - |
Fisogatinib | FGFR4 | - |
Ligand trap and antibodies | ||
FP-1039 | FGF2 | - |
FPA114 | FGFR2-IIb | - |
MFGR1877S | FGFR3 | - |
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Astolfi, A.; Pantaleo, M.A.; Indio, V.; Urbini, M.; Nannini, M. The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor. Int. J. Mol. Sci. 2020, 21, 3313. https://doi.org/10.3390/ijms21093313
Astolfi A, Pantaleo MA, Indio V, Urbini M, Nannini M. The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor. International Journal of Molecular Sciences. 2020; 21(9):3313. https://doi.org/10.3390/ijms21093313
Chicago/Turabian StyleAstolfi, Annalisa, Maria Abbondanza Pantaleo, Valentina Indio, Milena Urbini, and Margherita Nannini. 2020. "The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor" International Journal of Molecular Sciences 21, no. 9: 3313. https://doi.org/10.3390/ijms21093313