Targeting KIT

    • Activating mutations in KIT are associated with GIST, testicular seminoma, mast cell disease, melanoma, and acute myeloid leukemia, whereas inactivating mutations are associated with the genetic defect piebaldism.
    • Primary KIT mutations in exon 11 are the most common mutations in GIST patients and are associated with greater response to KIT-inhibitor imatinib, whereas mutations in exon 9 are associated with intrinsic resistance to imatinib.
    • Secondary mutations in the kinase domain of KIT are associated with acquired resistance to imatinib (exons 13–18).
    • Sunitinib can be used for the treatment of imatinib-resistant KIT. Its primary mutations in exon 9 and secondary mutations in exon 13 or 14 having greatest benefit.
    Other topics in Molecular Targets and Pathways