Proto-oncogene receptor tyrosine-protein kinase Kit (c-Kit)

Proto-oncogene receptor tyrosine-protein kinase Kit (c-Kit, CD117) is a transmembrane receptor tyrosine kinase of the type III family that binds stem cell factor (SCF, also called Kit ligand/KITLG). It comprises five extracellular immunoglobulin-like domains, a single transmembrane segment, a juxtamembrane region, and a cytoplasmic kinase domain. c-Kit is expressed on hematopoietic stem and progenitor cells, mast cells, melanocytes, germ cells, interstitial cells of Cajal, and other cell types. It mediates crucial roles in cell survival, proliferation, and differentiation in multiple tissues. Activating mutations or overexpression of c-Kit drive various cancers, most notably gastrointestinal stromal tumors (GISTs), certain leukemias, and mastocytosis, making the receptor an established clinical therapeutic target. Clinically, small-molecule tyrosine kinase inhibitors such as imatinib are used to treat KIT-driven cancers, though resistance mutations frequently emerge, necessitating alternative inhibitors or combinatorial therapies. c-Kit’s cell surface expression (CD117) is used as a diagnostic and prognostic biomarker. Its inhibition can affect normal stem cell function, pigmentation, fertility, and GI motility, representing key safety considerations for targeted therapies[1][3][4][5][2][7].

Other names

c-KitCD117KITStem cell factor receptor

Inhibition of tyrosine kinase activity (by small molecule inhibitors such as imatinib, sunitinib, regorafenib, etc.) Antibody-mediated inhibition or depletion (rare/experimental) Combination regimens including tyrosine kinase inhibitors and targeted antibodies (in development/precision medicine approaches)