Steroid hormones are key factors in breast and prostate tumor growth. The actions of the steroids are mediated by steroid hormone receptors, members of the nuclear receptor family of ligand-activated transcription factors. The types and magnitude of the activities of the receptors are dependent upon the cohort of coactivators, corepressors, and activity of cell signaling pathways in the cell; these factors and their interaction with receptors are potential therapeutic targets. Hormone ablation and/or anti-hormone therapies are commonly used to treat the cancers. However, tumors become resistant to these treatments. Although it was initially assumed that the resistant tumors had bypassed the requirements for the steroid receptors, there is exciting new data indicating that these tumors remain receptor-dependent and that alterations in receptor expression, coregulator expression and/or cell signaling permit the receptors to continue to function in the absence of physiological levels of androgens or estrogens. Consequently, the contribution of steroid receptor action in hormonally regulated tumors is greater than initially realized and raises a new set of questions regarding how to block the receptor activity. That the question of receptor actions in tumors is currently of high priority is supported by at least four RFAs related to this topic in the last few years and plans for two limited NIH workshops in 2004 addressing portions of these questions. There are many parallels between steroid action in breast and prostate. This program is unique in providing an opportunity to compare the actions in the two tumors with the goal of providing new opportunities for therapies. Bringing together investigators with expertise in receptors and their regulatory pathways with those who study breast and prostate cancer is important in facilitating progress in this area. Importantly, it will aid in introducing graduate students and post-doctoral fellows interested in this area to the major questions in this high priority field as well as giving them an opportunity to present there own work and to discuss it with leaders in the field.

R13CA112924

2005-02-18

2006-01-31