Protein tyrosine kinases (PTKs) are key enzymes of cellular signaling, regulating key processes such as proliferation, differentiation, migration, metabolism, and apoptosis. Tyrosine kinases (TKs) modulate protein functions in normal and disease states by phosphorylation of tyrosine residues on target proteins. In this critical role, dysregulation of TKs is directly linked with disease progression, particularly in cancer, therefore making TKs an attractive target for therapeutic intervention. The PTK family is broadly classified into receptor TKs (RTKs) and non-receptor TKs (NRTKs), having variation at both structural and functional levels. RTKs are membrane-bound kinases that initiate intracellular signaling when they react with extracellular ligands, whereas NRTKs within the cytoplasm or nucleus convey intracellular signaling upon receptor activation. This paper aims to review the organization, mechanistic activity, and therapeutic potential of PTKs, with a particular focus on epidermal growth factor receptor and proto-oncogene tyrosine-protein kinase (Src) as representatives of RTK and NRTK, respectively. In addition, this review also focuses on addressing emerging strategies to enhance tyrosine kinase inhibitor efficacy and overcome acquired resistance in cancer therapy.
Nadendla et al. (Wed,) studied this question.