Exploring the FGF/FGFR System in Ocular Tumors: New Insights and Perspectives

Abstract

Ocular tumors are a family of rare neoplasms that develop in the eye. Depending on the type of cancer, they mainly originate from cells localized within the retina, the uvea, or the vitreous. Even though current treatments (e.g., radiotherapy, transpupillary thermotherapy, cryotherapy, chemotherapy, local resection, or enucleation) achieve the control of the local tumor in the majority of treated cases, a significant percentage of patients develop metastatic disease. In recent years, new targeting therapies and immuno-therapeutic approaches have been evaluated. Nevertheless, the search for novel targets and players is eagerly required to prevent and control tumor growth and metastasis dissemination. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system consists of a family of proteins involved in a variety of physiological and pathological processes, including cancer. Indeed, tumor and stroma activation of the FGF/FGFR system plays a relevant role in tumor growth, invasion, and resistance, as well as in angiogenesis and dissemination. To date, scattered pieces of literature report that FGFs and FGFRs are expressed by a significant subset of primary eye cancers, where they play relevant and pleiotropic roles. In this review, we provide an up-to-date description of the relevant roles played by the FGF/FGFR system in ocular tumors and speculate on its possible prognostic and therapeutic exploitation.

Role of Fibroblast Growth Factors in the Crosstalk of Hepatic Stellate Cells and Uveal Melanoma Cells in the Liver Metastatic Niche

“…This aspect should be addressed in future studies. In line with the results of the present study, Loda et al proposed FGF/FGFR-targeted therapies as an integrate approach that is suitable to treat UM with regard to both stromal and parenchymal compartments [ 45 ].…”

“…A recent and elegant review by Loda et al extensively summarized the relevant roles of FGF/FGFR signaling in ocular tumors, including UM [ 45 ]. As reviewed by Loda et al, the inhibition of FGF/FGFR signaling might also play an integral part in the tumor/stroma interaction as an anti-angiogenic strategy, given the importance of FGFs in neo-angiogenesis [ 45 ]. It is tempting to speculate whether FGF9 or other factors secreted by HSCs also have an impact on the angiogenesis of hepatic UM metastases.…”

Fibroblast Growth Factor-2 (FGF-2) Expression in Pterygia Using Cell Spot Arrays

“…FGF/FGFR signaling dysregulation is partially responsible for the progression of neoplastic diseases, but not diseases such as epithelial malignancies (carcinomas), chronic kidney disease (CKD) or even insulin resistance [ 19 , 20 , 21 ]. In their inherent form, a variety of activating FGFR germline mutations have been already detected [ 22 ]. FGF/FGFR deregulation negatively affects epithelial neoplastic transformation in ocular diseases and tumors [ 23 ].…”

FGF-trapping hampers cancer stem-like cells in uveal melanoma

“…The aberrant activation of the FGF/FGFR system is frequently observed in human cancers, affecting cell proliferation, differentiation, migration, and survival [ 13 ]. The constitutive activation of the FGF/FGFR system has been described in UM, where the overexpression of the ligands and/or receptors promotes an autologous loop of stimulation which sustains UM progression [ 14 – 17 ]. Recently, we have identified the novel small molecule NSC12 as a pan-FGF-trap able to bind to FGFs and prevent FGFR activation.…”