Development of a Potential Therapy for Prostate Cancer Based Upon the Androgen Receptor
Our aim is to design targeted therapies which will recognize and disable the androgen receptor when it is activated in the absence androgen.
|Project Leaders||Marianne Sadar|
US Army, Department of Defense
Androgen-independent prostate cancers differ from androgen-responsive prostate cancers as they do not respond to a reduction of male hormone levels, which is one method used to slow the growth of androgen-responsive prostate cancers. Currently, no effective therapies are available for androgen-independent prostate cancer. Therefore, it is critical 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 recently 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 also is linked to the growth of prostate cancer cells and is the basis for androgen withdrawal therapy for patients with prostate cancer. Work in our laboratory has yielded results verifying the existence of alternative mechanisms 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, or ARN) are produced in prostate cancer cells, they specifically prevent androgen-independent increases in prostate-specific antigen. These data provide the rationale for the studies proposed, which include testing whether decoy molecules will prevent or delay the progression of prostate cancer to androgen independence. The problem of how to deliver these therapeutic peptides to patients with systemic prostate cancer is another important area of this research. Through this work we aim to identify new treatments to prevent androgen-independent disease.
Select Publications by our Research Team
- Yang YC, Banuelos CA, Mawji NR, Wang J, Kato M, Haile S, McEwan IJ, Plymate S, Sadar MD. Targeting androgen receptor activation function-1 with EPI to overcome resistance mechanisms in castration-resistant prostate cancer. Clin Cancer Res. 2016 Sep 1;22(17):4466-77. PMID: 27140928
- Kato M, Banuelos CA, Imamura Y, Leung JK, Caley DP, Wang J, Mawji NR, Sadar MD. . Clin Cancer Res. 2015 Dec 28. pii: clincanres.2119.2015.
- Myung JK and Sadar MD. Proteomics and Prostate Cancer in Genomics and Proteomics. Concepts, Technologies and Applications. Eds, Thangadurai D and Sangeetha J. Bioscience Publications. 2015. pp 143-187
- Martin S, BanuelosCA, Sadar MD, Kyprianou N. N-Terminal Targeting of Androgen Receptor Variant Enhances Response of Castration Resistant Prostate Cancer to Taxane Chemotherapy. Molecular Oncology. 2015 March 31; 9(3):628-639. 2014 Nov 15. pii: S1574-7891(14)00263-4. doi: 10.1016/j.molonc.2014.10.014.
- BanuelosCA, Lal, A, Tien AH, Shah N, Yang YC, Mawji NR, Meimetis LG, Park J, Kunzhong J, Andersen RJ, Sadar MD. Characterization of niphatenones that inhibit androgen receptor N-terminal domain. Plos One 2014 Sep 30;9(9):e107991
For all project related inquires please contact us.
Joanne Johnson, Projects Manager
Genome Sciences Centre, BC Cancer Agency
Phone: (604)675-8150 x 7901