Molecular mechanisms of chemoprevention and therapy of cancer by retinoids.

Chemoprevention is the use of noncytotoxic therapeutic intervention at the early stages of carcinogenesis against the development and progression of mutant clones to invasive cancer. Retinoids are the most extensively studied and one of the most prominent groups of chemopreventive agents to reach clinical trials. Acute promyelocytic leukemia is the first human malignancy that is successfully treated with all-trans retinoic acid. The t(15;17)(q22;q21) gene rearrangement and PML/RARalpha fusion product in acute promyelocytic leukemia played the key role to leukemogenesis and to sensitivity to differentiation-inducing therapy of all-trans retinoic acid. This review focuses on retinoid-based chemoprevention and therapy of cancer, and use acute promyelocytic leukemia as a model to illustrate the molecular mechanisms of retinoid signaling pathway.