Proto-oncogene tyrosine-protein kinase Src (SRC), Janus kinase 2 (JAK2), Insulin-like growth factor 1 receptor (IGF1R), and Epidermal growth factor receptor (EGFR) (SRC, JAK2, IGF1R, EGFR)

The target set comprising Proto-oncogene tyrosine-protein kinase Src (SRC), Janus kinase 2 (JAK2), Insulin-like growth factor 1 receptor (IGF1R), and Epidermal growth factor receptor (EGFR) represents a critical signaling network of tyrosine kinases frequently dysregulated in various malignancies [1, 3, 6]. EGFR and IGF1R are transmembrane receptor tyrosine kinases that initiate downstream signaling upon ligand binding, while SRC and JAK2 are non-receptor tyrosine kinases that mediate intracellular signal transduction and receptor transactivation [4, 9, 16]. These proteins exhibit extensive crosstalk; for instance, SRC and JAK2 can phosphorylate and activate EGFR and IGF1R independently of their ligands, contributing to oncogenic signaling and therapeutic resistance [9, 11, 15]. In clinical practice, the activation of IGF1R or SRC is a well-documented mechanism by which cancer cells bypass EGFR inhibition, leading to acquired resistance to drugs like erlotinib or osimertinib [1, 3, 7, 13]. Consequently, therapeutic strategies often involve combination regimens or multi-kinase inhibitors designed to simultaneously block these pathways to improve patient outcomes in cancers such as non-small cell lung cancer, colorectal cancer, and breast cancer [2, 5, 8, 12].

Other names

c-SrcJAK2IGF-1RErbB1HER1CD221JTK10JTK13

Inhibition of tyrosine kinase activity through competitive binding to the ATP-binding site (small molecule inhibitors) or by blocking ligand binding and receptor dimerization (monoclonal antibodies).