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Review
. 2020 Dec 18;12(12):3825.
doi: 10.3390/cancers12123825.

Role of Fibroblast Growth Factors Receptors (FGFRs) in Brain Tumors, Focus on Astrocytoma and Glioblastoma

Alessio Ardizzone  1 , Sarah A Scuderi  1 , Dario Giuffrida  2 , Cristina Colarossi  2 , Caterina Puglisi  3 , Michela Campolo  1 , Salvatore Cuzzocrea  1 , Emanuela Esposito  1 , Irene Paterniti  1
Affiliations
Review

Role of Fibroblast Growth Factors Receptors (FGFRs) in Brain Tumors, Focus on Astrocytoma and Glioblastoma

Alessio Ardizzone et al. Cancers (Basel). .

Abstract

Despite pharmacological treatments and surgical practice options, the mortality rate of astrocytomas and glioblastomas remains high, thus representing a medical emergency for which it is necessary to find new therapeutic strategies. Fibroblast growth factors (FGFs) act through their associated receptors (FGFRs), a family of tyrosine kinase receptors consisting of four members (FGFR1-4), regulators of tissue development and repair. In particular, FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, thus their gene alteration is certainly related to the development of the most common diseases, including cancer. FGFRs are subjected to multiple somatic aberrations such as chromosomal amplification of FGFR1; mutations and multiple dysregulations of FGFR2; and mutations, translocations, and significant amplifications of FGFR3 and FGFR4 that correlate to oncogenesis process. Therefore, the in-depth study of these receptor systems could help to understand the etiology of both astrocytoma and glioblastoma so as to achieve notable advances in more effective target therapies. Furthermore, the discovery of FGFR inhibitors revealed how these biological compounds improve the neoplastic condition by demonstrating efficacy and safety. On this basis, this review focuses on the role and involvement of FGFRs in brain tumors such as astrocytoma and glioblastoma.

Keywords: Fisogatinib; Futibatinib; astrocytoma; brain tumors; fibroblast growth factors (FGFs); fibroblast growth factors receptors (FGFRs); glioblastoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Classification of the main brain tumors; the tumors involved in this review are highlighted in red.
Figure 2
Figure 2
FGF/FGFR signaling pathway and its involvement in brain tumors. FRS2, fibroblast growth factor receptor substrate 2; GRB, growth factor receptor bound protein 2; SOS, son of sevenless; RAS, monomeric G-protein; RAF, kinase; MEK, kinase; MKP1, MAP kinase phosphatase; PIP2, phosphatidylinositol (4,5)-bisphosphate; PLCγ, phospholipase C γ; IP3, inositol triphosphate; DAG, diacylglycerol; PKC, protein kinase C.
Figure 3
Figure 3
Chemical structure of Fisogatinib (BLU-554) and its properties.
Figure 4
Figure 4
Chemical structure of futibatinib (TAS-120) and its properties.
See this image and copyright information in PMC

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