June 15, 2010, Vancouver, B.C. – Scientists in B.C. have developed a unique experimental drug, EPI-001, that shrinks prostate cancer tumours in the lab. The breakthrough came from the research groups of Dr. Marianne Sadar, Senior Scientist, BC Cancer Agency, an agency of the Provincial Health Services Authority, and Dr. Raymond Andersen, Professor, University of British Columbia. EPI-001 targets a protein believed responsible for the fatal progression of advanced stage prostate cancer.
The research, published today in Cancer Cell, is groundbreaking. Dr. Sadar’s team countered the findings of other scientists who were focused on one area of the androgen receptor protein. Dr. Sadar believed that an area at the opposite end of the protein structure, the N-terminal, was the true “engine” and should be targeted. In 2007, she made the discovery that the N-terminal was in fact implicated in advanced prostate cancer.
Based on this discovery, Drs. Sadar and Andersen collaborated to find a drug that would work on this target to delay or prevent the growth of prostate cancer. Thousands of marine natural products, known as potential leads for the development of anticancer drugs, were collected by Dr. Andersen’s team and screened to discover EPI-001, which is the first drug candidate in the world developed to target the N-terminal of the androgen receptor.
“What is remarkable about EPI-001 is that when used in laboratory conditions, it caused prostate cancer tumours to shrink”, says Dr. Sadar. “Testing in the lab showed no apparent toxicity.” Dr. Sadar notes that while the initial lab results are promising human clinical trials need to be undertaken and the results of any human trials may not be available for years.
Current drug therapies for advanced prostate cancer all target the opposite end of the androgen receptor, away from the “engine”. While initially effective in slowing tumour growth, these therapies are not curative. For this reason, EPI-001 is drawing attention from the international medical community.
“Dr. Sadar’s discovery is important because her inhibitor blocks the activating function of the androgen receptor by a mechanism that is independent of androgens. This inhibition is different from other clinically used antiandrogens, which inhibit the binding of androgens to the androgen receptor. Thus, EPI-001 may be effective for treating prostate cancers that have escaped hormonal therapy,” explains Dr. Donald J. Tindall, Director of the Prostate Cancer Program at the Mayo Clinic Cancer Center.
There is an urgent need to find new treatments for fatal prostate cancer. On average, 20 per cent of patients with prostate cancer have recurrence, and current drug therapies are not curative. Globally, in 2007, it was estimated that more than a quarter of a million men died from prostate cancer.
Dr. Bruce Montgomery, Associate Professor and Head of Prostate Cancer Research at the University of Washington, specializes in clinical trials for new cancer treatments. ”EPI-001 is an entirely novel means of inhibiting the androgen receptor, which remains the most important target for the treatment of advanced prostate cancer. EPI-001 effectively targets hormone sensitive cancers and is perhaps most exciting because it could potentially deal with all of the most important mechanisms of resistance which prostate cancer can generate to hormonal therapy. The discovery of these sorts of agents is why it is so exciting to be part of prostate cancer research today,” says Dr. Montgomery.
The equipment required to screen the compounds was made possible by donations. “The importance of the donor dollars invested in this groundbreaking research at the BC Cancer Agency cannot be overstated," says Douglas Nelson, President and CEO, BC Cancer Foundation. "We are extremely grateful to the Country Meadows Senior Men’s Charity Golf Classic and the Fore P.A.R. Charity Golf Classic who have supported Dr. Sadar's research through the BC Cancer Foundation for many years.”
The research was supported by peer-reviewed grant funds from the Canadian Institutes of Health Research, the National Cancer Institute of Canada and the U.S. Army Medical Research and Materiel Command Prostate Cancer Research Program.
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BC Cancer Agency