The stem cell factor receptor/c-Kit as a drug target in cancer.
Tyrosine phosphorylation has a key role in intracellular signaling. Inappropriate proliferation and survival cues in tumor cells often occur as a consequence of unregulated tyrosine kinase activity. Much of the current development of anti-cancer therapies tries to target causative proteins in a specific manner to minimize side-effects. One attractive group of target proteins is the kinases. c-Kit is a receptor tyrosine kinase that normally controls the function of primitive hematopoietic cells, melanocytes and germ cells. It has become clear that uncontrolled activity of c-Kit contributes to formation of an array of human tumors. The unregulated activity of c-Kit may be due to overexpression, autocrine loops or mutational activation. This makes c-Kit an excellent target for cancer therapies in these tumors. In this review we will highlight the current knowledge on the signal transduction molecules and pathways activated by c-Kit under normal conditions and in cancer cells, and the role of aberrant c-Kit signaling in cancer progression. Recent advances in the development of specific inhibitors interfering with these signal transduction pathways will be discussed.
Lennartsson
J
J
Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24 Uppsala, and Department of Laboratory Medicine, Lund University, Malmö University Hospital, Sweden.
Rönnstrand
L
L
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D019009:Proto-Oncogene Proteins c-kit