KIT (also called CD117), is a receptor tyrosine kinase (RTK) expressed on a wide variety of cell types. The ligand for KIT is stem cell factor (SCF). The binding of SCF to the extracellular domain of KIT induces receptor dimerization and activation of downstream signaling pathways, including the PI3K-AKT-mTOR pathway, the RAS-RAF-MEK-ERK pathway, and the STAT3 (signal transducer and activator of transcription 3 (acute-phase response factor)) pathway, all of which are involved in mediating pro-growth and pro-survival signals within the cell (Figure 1).
The discovery of KIT mutations revolutionized the treatment of GISTs. The use of imatinib mesylate (Gleevec, Novartis, Basel), an oral KIT inhibitor leads to rapid, substantial, and durable tumor responses (Demetri et al. 2002). Not all KIT mutations are associated with equal sensitivity to imatinib (Heinrich et al. 2008); some are more sensitive to second-generation KIT inhibitors.
Figure 1. Schematic of KIT signaling pathways. The binding of the ligand, stem cell factor (SCF), to the KIT receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK), the PI3K pathway (PI3K-AKT-mTOR), and the STAT3 (signal transducer and activator of transcription 3 (acute-phase response factor)) pathway. The letter "K" within the schema denotes the tyrosine kinase domain.
Suggested Citation: Lovly, C., J. Sosman, W. Pao. 2014. KIT. My Cancer Genome http://www.mycancergenome.org/content/disease/gist/kit/?tab=0 (Updated October 10).
Last Updated: October 10, 2014