Proto-oncogene tyrosine-protein kinase Src (SRC) (SRC)

Proto-oncogene tyrosine-protein kinase Src, commonly referred to as c-Src, is a non-receptor tyrosine kinase that functions as a central integrator of various intracellular signaling pathways [21, 26]. As the prototypical member of the Src family kinases (SFKs), it regulates fundamental cellular processes including proliferation, survival, migration, and cytoskeletal organization by phosphorylating a wide array of substrates [3, 21]. In human cancers, c-Src is frequently overexpressed or hyperactivated, which promotes tumor progression, epithelial-mesenchymal transition (EMT), and metastasis [23, 30]. It also plays a significant role in mediating resistance to other targeted therapies, such as EGFR and HER2 inhibitors, by providing bypass signaling routes [30, 32]. Beyond its oncogenic roles, c-Src is essential for bone homeostasis, specifically in the function of osteoclasts where it is required for the formation of the ruffled border and bone resorption [25, 34]. Consequently, c-Src has been explored as a therapeutic target for both advanced malignancies and metabolic bone diseases like osteoporosis [25, 27]. Small-molecule inhibitors such as dasatinib and bosutinib, which target the ATP-binding site of the kinase domain, are clinically approved for certain leukemias and have been extensively studied in solid tumors [38, 39]. However, the clinical efficacy of Src inhibitors as monotherapy in solid tumors has been modest, leading to a focus on combination strategies to enhance sensitivity and overcome drug resistance [23, 33].

Other names

c-Srcp60-Srcpp60c-srcSRC1ASVProto-oncogene c-SrcSRC proto-oncogene, non-receptor tyrosine kinase

ATP-competitive inhibition of the tyrosine kinase catalytic domain [28, 39, 40]