The FGF/FGFR/c-Myc axis as a promising therapeutic target in multiple myeloma.
C-Myc
FGF/FGFR system
Multiple myeloma
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
01 Nov 2024
01 Nov 2024
Historique:
received:
19
08
2024
accepted:
26
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
Among blood cancers, multiple myeloma (MM) represents the second most common neoplasm and is characterized by the accumulation and proliferation of monoclonal plasma cells within the bone marrow. Despite the last few decades being characterized by the development of different therapeutic strategies against MM, at present such disease is still considered incurable. Although MM is highly heterogeneous in terms of genetic and molecular subtypes, about 67% of MM cases are associated with abnormal activity of the transcription factor c-Myc, which has so far revealed a protein extremely difficult to target. We have recently demonstrated that activation of fibroblast growth factor (FGF) signaling protects MM cells from oxidative stress-induced apoptosis by stabilizing the oncoprotein c-Myc. Accordingly, secretion of FGF ligands and autocrine activation of FGF receptors (FGFR) is observed in MM cells and FGFR3 genomic alterations represent some 15-20% MM cases and are associated with poor outcome. Thus, FGF/FGFR blockade may represent a promising strategy to indirectly target c-Myc in MM. On this basis, the present review aims at providing an overview of recently explored connections between the FGF/FGFR system and c-Myc oncoprotein, sustaining the therapeutic potential of targeting the FGF/FGFR/c-Myc axis in MM by using inhibitors targeting FGF ligands or FGF receptors. Importantly, the provided findings may represent the rationale for using FDA approved FGFR TK inhibitors (i.e. Pemigatinib, Futibatinib, Erdafitinib) for the treatment of MM patients presenting with an aberrant activation of this axis.
Identifiants
pubmed: 39482742
doi: 10.1186/s13046-024-03217-2
pii: 10.1186/s13046-024-03217-2
doi:
Substances chimiques
Receptors, Fibroblast Growth Factor
0
Fibroblast Growth Factors
62031-54-3
Proto-Oncogene Proteins c-myc
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
294Informations de copyright
© 2024. The Author(s).
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