Tyrosine kinase (TK) (TK)

Tyrosine kinases (TKs) are a large family of enzymes that catalyze the transfer of a phosphate group from ATP to tyrosine residues on substrate proteins, serving as critical mediators of intracellular signaling pathways [1]. In oncology, these kinases are frequently dysregulated through mechanisms such as gene amplification, point mutations, or chromosomal translocations, leading to constitutive activation that drives uncontrolled cell proliferation, survival, and angiogenesis [2, 4]. They are broadly classified into receptor tyrosine kinases (RTKs), which are membrane-bound and respond to extracellular ligands, and non-receptor tyrosine kinases (nRTKs), which are located in the cytoplasm or nucleus [1, 5]. Tyrosine kinase inhibitors (TKIs) have become a cornerstone of targeted cancer therapy, designed to block the ATP-binding site or allosterically inhibit the enzyme's activity [3, 5]. While these drugs have significantly improved outcomes for patients with specific genetic drivers, their efficacy is often limited by the development of acquired resistance mutations and systemic toxicities, such as cardiotoxicity and skin reactions, resulting from the inhibition of kinases in non-malignant tissues [2, 5].

Other names

Protein-tyrosine kinasePTKReceptor tyrosine kinaseNon-receptor tyrosine kinaseOncology-relevant tyrosine kinases

Tyrosine kinase inhibitors primarily function through competitive inhibition of the ATP-binding site within the catalytic domain of the enzyme, thereby preventing the phosphorylation of tyrosine residues on substrate proteins and halting downstream signaling cascades [3, 5]. Some inhibitors also act through allosteric mechanisms or by stabilizing the kinase in an inactive conformation [5].