Review of the hair follicle origin hypothesis for basal cell carcinoma.
BACKGROUND
Basal cell carcinoma (BCC) is the most common type of skin cancer treated by the dermatologic surgeon. The discovery that patients with the nevoid BCC syndrome had mutations in the human homologue of the Drosophila patched gene led to a rapid increase in our understanding of the pathogenesis of BCC. It is theorized that altered regulation at multiple steps in the patched signal transduction pathway may contribute to the development of BCC. This pathway also plays an essential role in embryonic hair follicle development and during the hair cycle. Taken together, a considerable body of evidence suggests that at least some BCC may be derived from deregulated patched signaling in hair follicle stem cells.


OBJECTIVE
To review evidence of a follicular derivation of BCC and to highlight emerging therapeutic strategies to block deregulated patched signaling in BCC.


CONCLUSIONS
Deregulation of the patched signal transduction pathway is present in the vast majority of human BCCs. Pharmacologic inhibitors of this pathway may offer a therapeutic strategy to block tumor growth. The author has indicated no significant interest with commercial supporters.
Donovan
Jeff
J
Division of Dermatology, University of Toronto, Toronto, Ontario, Canada. jeffrey.donovan@utoronto.ca
D000818:Animals; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014704:Veratrum Alkaloids / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D014704:Veratrum Alkaloids; C000541:cyclopamine