Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jul 12;7(28):44735-44762.
doi: 10.18632/oncotarget.8203.

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

Mohamed R Akl  1 , Poonam Nagpal  1 , Nehad M Ayoub  2 , Betty Tai  1 , Sathyen A Prabhu  1 , Catherine M Capac  1 , Matthew Gliksman  1 , Andre Goy  3 , K Stephen Suh  1
Affiliations
Review

Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

Mohamed R Akl et al. Oncotarget. .

Abstract

Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies.

Keywords: FGF2; bFGF; diagnosis; malignancy; prognosis.

PubMed Disclaimer

Conflict of interest statement

There is no conflict of interest.

Figures

Figure 1
Figure 1. Model for FGF2/FGFR signaling and FGF2 binding partners
A. Structure of activated FGFR and downstream signaling B. FGF2 soluble and membranous binding partners.
Figure 2
Figure 2. FGF2/FGFR signaling in cancer
A. Model for FGF2/FGFR function under normal and cancer conditions B. Paracrine and autocrine signaling of FGF2 in tumor microenvironment.
Figure 3
Figure 3. Putative signaling pathways related to FGF2 in Hodgkin's lymphoma
Figure 4
Figure 4. FGF2/FGFR signaling inhibitors in cancer
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Powers C, McLeskey S, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer. 2000;7:165–197. - PubMed
    1. Korc M, Friesel RE. The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets. 2009;9:639. - PMC - PubMed
    1. Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8:235–253. - PMC - PubMed
    1. Florkiewicz RZ, Sommer A. Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons. Proc Natl Acad Sci U S A. 1989;86:3978–3981. - PMC - PubMed
    1. Ibrahimi OA, Zhang F, Eliseenkova AV, Linhardt RJ, Mohammadi M. Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity. Hum Mol Genet. 2004;13:69–78. - PubMed

MeSH terms

Substances