Applications for retinoids in cancer therapy

Current data suggest that the spectacular responses seen with the single-agent use of all-trans RA in APL will probably not be replicated in other diseases in the near future. Nonetheless, that experience has revealed critical information that ultimately may be generalizable to other types of cancer. Among these lessons include the observation that in APL the t(15;17) translocation appears to dominate other cytogenetic lesions, such that therapy directed against that lesion corrects the leukemic process, irrespective of the presence of other abnormalities. In addition, the concept of induced cytodifferentiation as a practical and consistently successful method of cancer treatment has been validated. Although all-trans RA itself may not prove as useful in other diseases, it is not unreasonable to expect that other retinoids (or ligands of other nuclear receptors used alone or in combination) may be effective. Finally, although the expectation of cure in patients with advanced cancers may never be realized with these compounds, they have distinct activity as cancer chemopreventive drugs, and widespread clinical testing is ongoing. Perhaps more than any other therapy, this preventive indication affords the greatest opportunity to impact favorably on public health.