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.
The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency. www.bccancer.bc.ca
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- Recent worldwide statistics estimate that there are approximately 782,647 new cases of prostate cancer and that more than a quarter of a million men die from the disease each year.
- In BC, an estimated 11,400 men will be diagnosed with some form of cancer in 2010 , and approximately 3,100 of these cases will be prostate cancer.
- Current drug therapies for castration-recurrent prostate cancer (CRPC) are not curative and are only able to slow tumour growth.
- CRPC is the fatal stage of the disease.
- The drug development is based on Dr. Sadar’s prior discoveries around the role of the N-terminal of the androgen receptor in the development of CRPC.
- Dr. Raymond Andersen, Professor of Chemical and Geochemical Oceanography with the Dept. of Earth and Ocean Sciences, University of British Columbia, is a world expert in the discovery of natural compounds. Together with Dr. Sadar, their labs worked together to isolate and test compounds from his library against the N-terminal of the androgen receptor.
- EPI-001 is the first drug candidate in the world developed to target the N-terminal (engine) of the androgen receptor.
- EPI-001 is being developed to treat CRPC by blocking the N-terminal, which inhibits androgen receptor activities including recently discovered constitutively active truncated splice variants for which there were no inhibitors until EPI-001.
- EPI-100 has proven to reduce, and potentially cure CRPC in xenografts with very limited toxicity and side-effects.
- EPI-001 is a small molecule drug that is being developed for clinical trials.