Project Leader

Donald Muccio, Ph.D.

Co-Investigators
Kirby I. Bland, M.D.
Wayne J. Brouillette, Ph.D.
Clinton J. Grubbs, Ph.D.
Donald H. Hill, Ph.D.
Ruiwen Zhang, M.D., Ph.D.

With the success of anti-estrogens as a major therapeutic modality in various stages of breast cancer, the role of anti-estrogens in chemoprevention has assumed a prominent role in the management of high-risk patients. However, the use of anti-estrogens in chemoprevention therapy is not without limitations and risks, thus, new chemoprevention agents that are more effective and less toxic are needed. In vivo studies have shown that 9-cis-retinoic acid (9cRA) of related retinoids selectively interact with nuclear retinoid X receptors (RXRs) tamoxifen or raloxifene. At UAB, we have designed and synthesized two new classes of RXR-selective retinoids. We have already shown, for example, that 9cUAB30, is effective in in vivo efficacy models. These studies will: (a) determine the optimal dose of RXR-selective retinoids for mammary cancer prevention model, (b) determine if the combination of 9cUAB30 with other non-steroidal estrogen response modifiers, like tamoxifen, are additive or lead to synergistic prevention of mammary cancer, and (c) determine potential surrogate endpoint biomarkers. The demonstration that these retinoids are effective would lead to evaluating their toxicity (to determine a therapeutic index) and pharmacology. A diverse and effective team of scientists has been assembled with extensive expertise in retinoid research and clinical experience to move promising UAB retinoids to Phase I clinical trials.