Presently, the only effective therapy for advanced prostate cancer is to reduce patients' levels of testosterone (androgen). Unfortunately, androgen withdrawal does not completely or permanently eliminate all prostate cancer cells, a prerequisite for a cure. Eventually the disease will return in an androgen-independent form. Once the malignancy is androgen-independent, it is able to grow in the absence of androgen. Currently, there are not any effective therapies available for androgen-independent disease. Therefore, it is critically important to identify the molecular mechanisms responsible for the ability of the cancer to grow in the absence of androgen so that new therapies can be developed. Our laboratory has identified a possible molecular mechanism that may underlie androgen-independent disease. This mechanism builds on pre-existing knowledge that androgen stimulates the growth of prostate cells by activating androgen receptors located in the cell. The activation of the androgen receptor is also linked to the growth of prostate cancer cells and is the basis for androgen withdrawal therapy for patients with prostate cancer. Work from our laboratory and others has yielded results verifying the existence of alternative pathways for activating the androgen receptor in the absence of androgens. We have identified a unique region on the androgen receptor, such that when many copies of this region (called decoy molecules) are produced in prostate cancer cells, they inhibit tumor growth and progression. This data provides the rationale for the studies proposed, which include reducing the size of decoy molecules to the essential region and identifying the potential mechanism of how they work. The capability of decoy molecules to block prostate cancer tumor growth and progression presents a new direction for the development of antagonists for the clinical management of this disease.