The Complexity and Significance of Fibroblast Growth Factor (FGF) Signaling for FGF-Targeted Cancer Therapies.

Simple Summary: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play a crucial role in cancer development. However, due to their diverse cellular functions, the mechanisms by which they drive cancer are complex. In this review, we discuss the mechanisms of action of FGFs and FGFRs, as well as how the dysregulation of FGF signaling contributes to cancer in various tumor types. The complexity of FGF signaling is partly explained by the large number of FGF isoforms and FGFR receptor types. We provide a classification of FGF ligands based on their signaling modes and binding specificity to FGFRs. Additionally, we explore promising therapeutic strategies being developed to target FGF signaling in oncology, including small molecules, ligand traps, and monoclonal antibody-based inhibitors. Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 subfamily is particularly interesting because of its unique protein structure and role in endocrine function. The abnormal expression of FGFs in different cancer types (breast, colorectal, hepatobiliary, bronchogenic, and others) is examined and correlated with patient prognosis. The classification of FGF ligands based on their mode of action, whether autocrine, paracrine, endocrine, or intracrine, is illustrated, and an analysis of the binding specificity of FGFs to FGFRs is also provided. Moreover, the latest advances in cancer therapeutic strategies involving small molecules, ligand traps, and monoclonal antibody-based FGF inhibitors are presented. Lastly, we discuss how the dysregulation of FGF and FGFR expression affects FGF signaling and its role in cancer development. [ABSTRACT FROM AUTHOR]