Sci. STKE, 28 October 2003
PHARMACOLOGY Cancer Treatment Changes Hair Color
Kinases are appealing targets in the battle against cancer because in many cases their activity is increased in the cancerous cells or their activity is required for such cancer cell survival processes as the growth of new blood vessels into the tumor. KIT is a receptor tyrosine kinase that is one of the kinases inhibited by drugs already in the clinic, such as Gleevec, and is one target of other kinase inhibitors still in development. KIT and its ligand stem cell factor are known to be essential for proper hair pigmentation, and mutations in their encoding genes are associated with various hair pigmentation phenotypes. Moss et al. reported that mice receiving oral SU11248, a kinase inhibitor undergoing Phase I clinical trials, or injections of an antibody that neutralizes KIT activity exhibited dose-dependent loss of hair pigmentation. The depigmentation was reversible with cessation of treatment. Histochemical analysis demonstrated that there was no loss of KIT-positive melanocytes in the hair follicles. Furthermore, human subjects in the Phase I trial also reported hair depigmentation patterns that correlated with the duration of treatment. Thus, hair depigmentation may serve as a noninvasive readout of the effectiveness of kinase inhibitors for the KIT receptor.
K. G. Moss, G. C. Toner, J. M. Cherrington, D. B. Mendel, A. D. Laird, Hair depigmentation is a biological readout for pharmacological inhibition of KIT in mice and humans. J. Pharmacol. Exp. Ther. 307, 476-480 (2003). [Abstract] [Full Text]
Citation: Cancer Treatment Changes Hair Color. Sci. STKE 2003, tw420 (2003).
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