The Role of Fibroblast Growth Factor-Receptor Pathway Aberrations in Pediatric Diseases

Abstract

The fibroblast growth factor receptors play a crucial role in binding to fibroblast growth factor and are involved in various pathological conditions. These receptors consist of an extracellular ligand domain, a transmembrane helix domain, and an intracellular domain with tyrosine kinase activity. There are over 48 different isoforms of FGFR. Each FGF receptor in ligand-binding properties and kinase domains. The FGF/FGFR signaling pathway is implicated in various pediatric cancers and therefore are both non-selective and selective FGFR inhibitors available. Additionally, there are five distinct membrane FGF receptors dentified in vertebrates. All belonging to the tyrosine kinase superfamily. In this manuscript, the focus is based on an analysis of the role of FGF receptor signaling pathways and aberrations especially in pediatric diseases. Erk 1 and Erk 2 seem to have an important role as a mediator of FGF signaling in different biological and developmental processes. FGF signaling plays an important role in conserved developmental functions in skeletal growth, palate closure, ear development, cranial suture ossification and neuronal development in the child. Aberrant FGF signaling causes different congenital disorders and different forms of cancer in childhood. Modulating FGF signaling is of great importance for the treatment of rare diseases in childhood.