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 and K. Stephen Suh 1 1 Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA 2 Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan 3 Lymphoma Division, The John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA Correspondence to: K. Stephen Suh, email: // Keywords : bFGF, FGF2, diagnosis, prognosis, malignancy, Received : October 20, 2015 Accepted : March 10, 2016 Published : March 19, 2016 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.