Receptor tyrosine kinase families: a central hub of cellular signaling and involvement in human health and disease

Receptor tyrosine kinases (RTKs) are single-pass transmembrane receptors important for the regulation of intercellular communications, controlling cell growth, proliferation, differentiation, survival, and metabolism. There are 58 members of RTKs in the human genome, divided into 20 families. RTKs bind to extracellular polypeptide ligands, mainly growth factors. Abnormal activation of RTKs has been repeatedly observed and recognized as a contributing factor in the progression of various diseases such as cancer and some congenital conditions. Understanding the precise structural mechanisms by which ligands and cofactors induce RTK oligomerization and activation is crucial for elucidating disease mechanisms and identification, providing potential novel avenues for intervention. In this review, we provide an overview of the detailed molecular and functional characteristics of RTKs and their signaling. We also discuss the evolution of RTKs and the construction of the human RTK phylogenetic tree. Moreover, the factors contributing to their dysregulation and disease associations are highlighted. Furthermore, we discuss recent advances in currently available targeted therapies, including investigational and preclinical potential therapies, highlighting key challenges and insights into future directions for RTK-targeted treatments.