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Tyrosine kinase inhibition and grey hair

2003; Elsevier BV; Volume: 361; Issue: 9362 Linguagem: Inglês

10.1016/s0140-6736(03)12805-x

1474-547X

Caroline Robert, Alan Spatz, Sandrine Faivre, Jean‐Pierre Armand, Eric Raymond,

Hair Growth and Disorders

Repigmentation of grey hair has been reported in nine of 133 patients treated with the tyrosine kinase inhibitor imatinib (STI571).1Etienne G Cony-Makhoul P Mahon FX Imatinib mesylate and gray hair.N Engl J Med. 2002; 347: 446Crossref PubMed Scopus (7) Google Scholar Although the molecular mechanisms involved are unknown, they could be related to blocking of c-KIT, since imatinib inhibits this tyrosine kinase receptor and the related platelet-derived growth factor (PDGF) receptor.2Capdeville R Buchdunger E Zimmermann J Matter A Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug.Nat Rev Drug Discov. 2002; 1: 493-502Crossref PubMed Scopus (1219) Google Scholar Stimulation of c-KIT normally leads to short-lived activation followed by rapid degradation of the microphthalmia transcription factor (Mi), which transactivates the tyrosinase pigmentation gene promoter in melanocytes.3Hemesath TJ Price ER Takemoto C Badalian T Fisher DE MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes.Nature. 1998; 391: 298-301Crossref PubMed Scopus (545) Google Scholar, 4Wu M Hemesath TJ Takemoto CM et al.c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi.Genes Dev. 2000; 14: 301-312Crossref PubMed Google Scholar We have seen the opposite effect—ie, hair depigmentation—in patients with recurrent or metastatic cancers treated with the novel drug SU11428 (Sugen) during a phase 1 clinical trial. SU11428 is a new antiangiogenic oxindole that blocks the receptors for vascular endothelial growth factor (VEGF), PDGF, and stem-cell factor. Hair depigmentation was seen in 18 of 28 patients, irrespective of the origin of the primary cancer. It concerned all patients who received at least 50 mg of SU11428 per day, and who did not have grey hair before treatment. Depigmentation was detectable on all body hair after about 5–6 weeks of treatment. Microscopic examination of the hair showed that the pigment had disappeared without any other hair shaft abnormality. The process seemed to be reversible, since normally pigmented hair growth was visible in several patients as early as 3 weeks after treatment discontinuation. Blocking of various combinations of three tyrosine kinase receptors can result in very different effects on hair pigmentation. These observations suggest that further studies of these three signalling pathways might lead to important steps towards elucidating the complex molecular events involved in melanocyte differentiation.