Abstract / Summary
Receptor tyrosine kinases (RTKs), constituting a major family of cell-surface transmembrane receptors, are essential for intracellular tyrosine phosphorylation and signal transduction. RTK signaling is crucial for cellular fate regulation and tissue homeostasis, and its disruption is linked to numerous diseases. Herein, we present a comprehensive review of signaling pathways involving RTKs, with a focus on their signal transduction mechanisms and key components, along with their interactions with major signaling cascades such as G protein-coupled receptors, Wnt, and transforming growth factor β pathways. We also elucidate the multidimensional roles of RTKs in cancer development and progression, highlighting their key effects on cancer stem cell maintenance, tumor microenvironment modulation, and other factors. Furthermore, we systematically summarize the roles of RTKs in noncancerous diseases, including cardiovascular disorders, neurodegenerative diseases, metabolic syndrome, autoimmune conditions, and fibrotic disorders. We then examine current RTK-targeted therapeutics, including small-molecule inhibitors and monoclonal antibodies, for the treatment of various cancers. Finally, novel therapeutic strategies, along with the challenges associated with their development and application, are discussed. In summary, this review will enhance the understanding of the mechanistic aspects of RTK signaling in major disease pathways and provide a detailed overview of recent advancements in targeted therapeutic interventions.