Retinoids and apoptosis in cancer therapy

Retinoids serve as physiologic and pharmacologic mediators of proliferation, differentiation and apoptosis in normal and malignant cell types. All-trans-retinoic acid (tRA), a natural metabolite of vitamin A, induces differentiation and subsequent apoptosis in several types of malignant cells with immature phenotypes. Clinically, tRA has been approved for the treatment of patients with acute promyelocytic leukemia. Several synthetic retinoids induce apoptosis without differentiation in a variety of malignant epithelial cells in vitro. The synthetic derivative, N-(4-hydroxyphenyl)retinamide (HPR), shows significant promise as a chemo-preventive and therapeutic anti-cancer agent in light of its minimal toxicity and broad activity in experimental cancer models representing common human malignancies. This paper reviews the role of retinoids as mediators of differentiation and apoptosis in malignant cells, and the impact this activity could have on clinical oncology.