The Emerging Role of the FGF/FGFR Pathway in Gastrointestinal Stromal Tumor

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 deh...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-05, Vol.21 (9), p.3313
Main Authors: Astolfi, Annalisa, Pantaleo, Maria Abbondanza, Indio, Valentina, Urbini, Milena, Nannini, Margherita
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Autocrine signalling
Binding sites
Clinical Trials as Topic
Deregulation
Drug Resistance, Neoplasm - drug effects
FGF4
FGFR1
Fibroblast growth factor receptors
Fibroblast Growth Factors - genetics
Gastrointestinal cancer
Gastrointestinal Neoplasms - drug therapy
Gastrointestinal Neoplasms - genetics
gastrointestinal stromal tumor
Gastrointestinal Stromal Tumors - drug therapy
Gastrointestinal Stromal Tumors - genetics
Gastrointestinal system
Gastrointestinal tract
Gene expression
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
GIST
Growth factors
Heparan sulfate
Humans
Immunoglobulins
Kinases
Ligands
Mesenchyme
Mutants
Mutation
Neoplasia
Neoplasms
Paracrine signalling
PDGFRA
Phosphorylation
Platelet-derived growth factor
Proteins
Receptors, Fibroblast Growth Factor - genetics
Review
Signal transduction
Signal Transduction - drug effects
Subgroups
Succinate dehydrogenase
Tumors
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Description
Summary: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 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 WT, SDH- , or KIT-mutant GISTs.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21093313