Jeff Donovan1. 1. Division of Dermatology, University of Toronto, Toronto, Ontario, Canada. jeffrey.donovan@utoronto.ca
Abstract
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. CONCLUSION: 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.
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 Drosophilapatched 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. CONCLUSION: 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.
Authors: Marina Grachtchouk; Joanna Pero; Steven H Yang; Alexandre N Ermilov; L Evan Michael; Aiqin Wang; Dawn Wilbert; Rajiv M Patel; Jennifer Ferris; James Diener; Mary Allen; Seokchun Lim; Li-Jyun Syu; Monique Verhaegen; Andrzej A Dlugosz Journal: J Clin Invest Date: 2011-04-25 Impact factor: 14.808
Authors: Tjinta Brinkhuizen; Karin van den Hurk; Véronique J L Winnepenninckx; Joep P de Hoon; Ariënne M van Marion; Jürgen Veeck; Manon van Engeland; Maurice A M van Steensel Journal: PLoS One Date: 2012-12-17 Impact factor: 3.240
Authors: N Rajan; R Elliott; O Clewes; A Mackay; J S Reis-Filho; J Burn; J Langtry; M Sieber-Blum; C J Lord; A Ashworth Journal: Oncogene Date: 2011-05-09 Impact factor: 9.867