Flexible receptor model explains structural determinants for agonist and antagonist activity in retinoid receptors

CAVASOTTO, CLAUDIO N.; ABAGYAN, RUBEN A.

Orlando, FL

Simposio; Era of Hope Meeting - DOD Breast Cancer Program; 2002

The most widely employed therapy against breast cancer is based on Estrogen Receptor (ER) modulators, which have undesirable side effects and are inefficacious against ER-negative breast cancer cells. Compounds targeted to the RRs, members of the Nuclear Receptor (NR) superfamily, are known to inhibit the growth of a wide variety types of cancer, including ER-positive and ER-negative breast cancer cells. RRs are divided into two sub-families, the RAR isotypes (a, b and g) and the Retinoic X Receptor isotypes (RXR a, b and g). Both agonists and antagonists of RAR can present anti-tumor activity against breast cancer and also RXR ligands appear to be also efficacious agents against breast cancer cells. Since RXR is also the obligate partner of many other NRs ?including itself-, understanding and controlling the structural mechanisms which govern RXR specificity and synergy will also help to design modulators with improved profile against breast cancer cells.