Retinoids and differentiation treatment: a strategy for treatment in cancer.

The retinoids are a large group of compounds structurally related to vitamin A. Retinoids elicit specific biological responses by binding to and activating nuclear receptors. Information about the metabolism and storage of vitamin A and retinoids, their plasma transport and uptake and the retinoid dose efficient on target cell had to be established because retinoic acid (RA), the natural acidic derivative of vitamin A (retinol), is likely to be a key factor during specific phases of embryonic development and maintenance of normal differentiated phenotypes in adult, so vitamin A is involved in the normal morphological differentiation of the visual system. RA appears an important agent since it induces in vitro leukemic cells from acute promyelocytic leukemia (APL) to differentiate into mature functional granulocytes which lose their self-renewal ability and die spontaneously. In vivo, APL patients treated with oral all-trans retinoic acid (all-trans RA) alone achieve complete remission in 80% of the cases. APL results from a malignant process that leads to the accumulation in the blood and in the bone marrow of myeloid precursor cells characterized by an abnormal behavior and a differentiation arrest. APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RARa gene on chromosome 17 and gives rise to the PML/RARa fusion protein. The high sensitivity of the promyelocytic blasts to all-trans RA should be related to the presence in APL blast of an abnormal protein, the PML/RAR alpha. The antineoplastic effects of retinoids suggest that these drugs could be used therapeutically for the chemoprevention of cancer.