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Molecular and Immunologic Techniques in a Genetically Engineered Mouse Model of Gastrointestinal Stromal Tumor
Published on: May 2, 2022
The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor
Annalisa Astolfi1, Maria Abbondanza Pantaleo2, Valentina Indio3
1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
Abstract:
Gastrointestinal stromal tumors (GIST) are rare neoplasms of mesenchymal origin arising in the gastrointestinal tract. The vast majority are characterized by mutually exclusive activating mutations in KIT or Platelet-derived growth factor alpha (PDGFRA) receptors, or less frequently by succinate dehydrogenase complex (SDH) or NF1 inactivation, with very rare cases harboring mutant BRAF or RAS alleles. Approximately 5% of GISTs lack any of such mutations and are called quadruple wild-type (WT) GISTs. Recently, deregulated Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) signaling emerged as a relevant pathway driving oncogenic activity in different molecular subgroups of GISTs. This review summarizes all the current evidences supporting the key role of the FGF/FGFR pathway activation in GISTs, whereby either activating mutations, oncogenic gene fusions, or autocrine/paracrine signaling have been detected in quadruple WT, SDH-deficient, or KIT-mutant GISTs.
Insights
Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) signaling drives oncogenic activity in gastrointestinal stromal tumors (GIST). This pathway is implicated in quadruple wild-type, SDH-deficient, and KIT-mutant GISTs, highlighting its therapeutic potential.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms.
- Most GISTs have KIT or PDGFRA mutations; others involve SDH, NF1, BRAF, or RAS.
- Quadruple wild-type (WT) GISTs lack these common mutations.
Purpose of the Study:
- To review current evidence on Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) pathway activation in GIST.
- To highlight the role of FGF/FGFR signaling in various GIST molecular subgroups.
Main Methods:
- Literature review of studies investigating GIST molecular alterations.
- Analysis of evidence linking FGF/FGFR pathway to GIST pathogenesis.
- Synthesis of findings across different GIST molecular subtypes.
Main Results:
- Deregulated FGF/FGFR signaling is a key driver in GIST oncogenesis.
- FGF/FGFR pathway activation is observed in quadruple WT, SDH-deficient, and KIT-mutant GISTs.
- Mechanisms include activating mutations, gene fusions, and autocrine/paracrine signaling.
Conclusions:
- The FGF/FGFR pathway is a critical oncogenic driver in diverse GIST subtypes.
- Targeting the FGF/FGFR pathway represents a potential therapeutic strategy for GIST patients.
- Further research is warranted to elucidate the full impact of FGF/FGFR signaling in GIST.
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