Receptor Tyrosine Kinase

Receptor Tyrosine Kinases (RTKs) are transmembrane proteins that regulate fundamental cellular processes including growth, differentiation, metabolism, and survival through signal transduction pathways initiated by extracellular ligand binding. These receptors possess intrinsic enzymatic activity, catalysing tyrosine phosphorylation on substrate proteins upon activation, making them critical nodes in cellular communication networks and highly valuable therapeutic targets.

The human genome encodes approximately 58 RTK genes, with prominent examples including epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptors (VEGFRs), and platelet-derived growth factor receptors (PDGFRs). RTKs typically exist as inactive monomers that dimerise upon ligand binding, triggering conformational changes enabling kinase domain activation. Aberrant RTK signalling contributes to numerous diseases, particularly cancer where mutations, overexpression, or autocrine loops drive uncontrolled proliferation. The biopharmaceutical industry has successfully targeted RTKs with multiple therapeutic modalities. Small-molecule tyrosine kinase inhibitors like imatinib, erlotinib, and sunitinib competitively inhibit ATP binding in kinase domains. Monoclonal antibodies including trastuzumab and cetuximab prevent ligand binding or promote receptor degradation. These RTK-targeted therapies have transformed oncology treatment, and ongoing research explores more selective inhibitors, combination strategies overcoming resistance mechanisms, and antibody-drug conjugates leveraging RTK expression for tumour-targeted delivery.