Classical and novel retinoids: their targets in cancer therapy.
Retinoids are important mediators of cellular growth and differentiation. Retinoids modulate the growth of both normal and malignant cells through their binding to retinoid nuclear receptors and their subsequent activation. While retinoids have demonstrated therapeutic efficacy in the treatment of acute promyelocytic leukemia, their spectrum of activity remains limited. Other agents such as histone deacetylase inhibitors may significantly increase retinoid activity in a number of malignant cell types. The novel retinoids N-(4-hydroxyphenyl) retinamide (4-HPR) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437; AHPN) induce apoptosis in a wide variety of malignant cells. Their mechanism(s) of action remain unclear, although a number of potential targets have been identified. Whether the retinoid receptors are involved in 4-HPR and CD473/AHPN mediated apoptosis remains unclear. Both 4-HPR and CD437/AHPN display significant potential as therapeutic agents in the treatment of a number of premalignant and malignant conditions.
Fontana
J A
JA
John D Dingell VA Medical Center and the Department of Medicine and Karmanos Cancer Institute, Wayne State University Detroit, MI 48201, USA.
Rishi
A K
AK
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017313:Fenretinide / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; C099555:CD 437; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D017313:Fenretinide