Retinoids: therapeutic applications and mechanisms of action in cutaneous T-cell lymphoma.
Retinoids, natural and synthetic derivatives of vitamin A, are biological regulators of differentiation, proliferation, apoptosis, and immune response. Retinoic-acid-receptor-selective retinoids (all-trans retinoic acid, 13-cis-retinoic acid, and the synthetic analogs isotretinoin, etretinate and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphoma (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid-X-receptor retinoid to be approved by the FDA for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Bexarotene treatment induces apoptosis of CTCL cells with down-regulation of its receptors and of survivin, an inhibitor of apoptosis. Identification of new receptor subtype-selective retinoids, combination of various receptor-selective retinoids or other agents, and a new drug delivery system may improve the clinical efficacy of retinoids in the future.
Zhang
Chunlei
C
Department of Dermatology, Division of Internal Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Duvic
Madeleine
M
D000287:Administration, Topical; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001707:Biopsy, Needle; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D012176:Retinoids / Q000008:administration & dosage*; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
D012176:Retinoids