Evolution of aerodigestive tract 13-cis-retinoid acid chemoprevention: the M.D. Anderson experience.

The ultimate goal of our chemoprevention research is to prevent or inhibit the development of aerodigestive cancer in humans. We have made substantial progress from our trials 10 years ago. The chemopreventive strategies utilized in our clinical trials involve the use of retinoids and carotenoids as chemopreventive agents. The choice of these agents was based upon their important anticarcinogenic and differentiation properties. It is important to understand how retinoids interact with cells to carry out their modulating activities, and we hope to increase our understanding through molecular analysis of retinoid receptors. In the case of aerodigestive epithelial tissues at risk, normal, non-keratinizing epithelial cells often express inappropriate squamous differentiation. Retinoids are thought to suppress premalignant lesions by suppressing these inappropriate squamous differentiation pathways. The role of retinoids in suppressing squamous differentiation markers and reversing premalignant lesions will be elucidated from this retinoid project. The development of a fundamental understanding of tumorigenesis in the aerodigestive tract can lead to novel preventive approaches. A relative degree of risk for cancer development in individuals depends on several components, including the extent of carcinogenic exposure, inherent sensitivity of the individual to carcinogens, the individual's nutritional status, etc. Individuals with a genetic component of increased carcinogen sensitivity appear to be at increased risk for developing primary and secondary tumors. Our chemoprevention research program is designed to develop innovative strategies for aerodigestive tract epithelial cancer prevention. The strength of our program is to bridge the gap between fundamental and cellular molecular studies in clinical chemoprevention trials. The outcome of our research efforts may have an enormous impact on public health in controlling aerodigestive epithelial cancers and other epithelial cancers as well.