Discovery of new drug candidates for the clinical management of prostate cancer
Our aim is to identify small molecules that may prevent or delay the progression of prostate cancer towards androgen-independent disease.
| Project Leaders | Marianne Sadar |
|---|---|
| Project Co-Investigators | Raymond Andersen, Yikan Wang |
| Involved Organizations |
Canada's Michael Smith Genome Science Centre
University of British Columbia
British Columbia Cancer Agency
|
| Funding Agencies |
Screening Robot
Overview
The goal of this research has been to screen and then test small molecules that may prevent or delay the progression of prostate cancer to androgen-independence. In the course of this work we have identified important lead compounds with potential to be used to develop new drugs that will delay or prevent the development of androgen independent prostate cancer.
Specific aims:
- Screen several small molecule libraries using a cell-based system to identify lead compounds or extracts that inhibit transactivation of N-terminus of the AR (androgen receptor)
- Isolate the pure active compound from the extracts
- Validate the lead compound by application of secondary screens
- Employ xenograft models and test whether the small molecules that inhibit activation of the androgen receptor in vitro have any effect on these tumors
Recent Publications by our Research Team:
- Leung JK and Sadar MD. Non-genomic actions of the androgen receptor in prostate cancer. Frontiers In Endocrinology. Published on-line January 4, 2017.
- Banuelos CA, Tavakoli I, Tien AH, Caley DP, Mawji NR, Li Z, Wang J, Yang YC, Imamura Y, Yan L, Wen JG, Andersen RJ, Sadar MD. Sintokamide A is a Novel Antagonist of Androgen Receptor that Uniquely Binds Activation Function-1 in its Amino-Terminal Domain. J Biol Chem. 2016 Oct 14;291(42):22231-22243. PMID: 27576691
- Imamura Y, Tien AH, Pan J, Leung JK, Banuelos CA, Jian K, Wang J, Mawji NR, Fernandez JG, Lin KS, Andersen RJ and Sadar MD. An imaging agent to detect androgen receptor and its active splice variants in prostate cancer. J. Clin. Invest. Insight. 2016;1(11):e87850. doi:10.1172/jci.insight.87850. PMID: 27525313
- Antonarakis ES, Chandhasin C, Osbourne E, Luo J, Sadar MD, Perabo F. Targeting the N-terminal domain of the androgen receptor: a new approach for the treatment of advanced prostate cancer. The Oncologist, 2016 Sep 14. pii: theoncologist.2016-0161. [Epub ahead of print]. PMID: 27628492
Contact Information
For all project related inquires please contact us.
Joanne Johnson, Project Manager
Genome Sciences Centre, BC Cancer Agency
Email: jjohnson@bcgsc.ca
Phone: 604-675-8000 x 7901
Fax: 604-675-8178