VANCOUVER - A scientist at the BC Cancer Agency has discovered a new route to solving the mystery of hormone-resistant prostate cancer and a therapeutic target for better treatments, according to a study published today in the Journal of Biological Chemistry.

"We know cancer cells find a variety of ways to get around drug therapies," says Dr. Marianne Sadar, the author of the paper. "This is the case in prostate cancer that no longer responds to hormone therapies. We've identified one of these maneuvers and it could lead to new ways to treat the disease."

The early stages of prostate cancer are governed by the growth-promoting activity of the male sex hormone testosterone. The study identifies how prostate cancer cells become resistant to therapy based on withdrawal of the hormone.

Scientists have known for some time that the action of the male sex hormone on prostate cells is mediated by an androgen receptor - a protein that is switched on when it binds to testosterone. The activation of the protein is a crucial event in the growth process of prostate cancer cells. Withdrawing testosterone prevents activation of the protein and forms the basis of hormone withdrawal therapy.

Sadar, a senior scientist at the BC Cancer Agency, has revealed a possible pathway through which prostate cancer cells switch on the activation of the protein, even without the hormone. Researchers and clinicians at the research and treatment organization are now studying ways to develop drugs that inhibit the development of hormone-resistant disease.

"The reason for the progression of prostate cancer to a therapy-resistant state is still unknown," says Dr. Victor Ling, vice-president of Research at the BC Cancer Agency. "This latest discovery brings us one step closer to unraveling the mystery of this complicated disease."

The BC Cancer Agency has made significant breakthroughs in prostate cancer research, early detection and treatment due to a renowned team of scientists under the leadership of Dr. Nicholas Bruchovsky.

"We're focusing our work on discovering how this type of cancer becomes resistant to hormonal withdrawal therapy," Bruchovsky says. "The loss of response to treatment is one of the major stumbling blocks that limits the effectiveness of today's therapies. Dr. Sadar's discovery has opened up a whole new approach to possible cures."

A scientist and clinician, Bruchovsky discovered in the early 1970s the biological importance of dihydrotestosterone, a derivative of testosterone, as the main stimulator of the growth of prostate cancer. He is heralded by his colleagues and patients as Canada's "father" of prostate cancer research and is a crusader for improved treatments. Bruchovsky, Sadar and Dr. Peter W. Gout are investigating this new focus in prostate cancer research.

Recognition of the importance of this work has come from American sources in the form of grants totaling more than $1million over five years.

Surgery and radiotherapy are effective treatments for localized prostate cancer, but are inadequate when the disease has spread throughout the body. The only useful therapy available for this stage of the disease is to reduce the levels of testosterone. However, most patients face a life-threatening problem: prostate cancer cells, at first responsive to treatment, evolve so that they can grow without the hormone and hence are resistant to further hormonal manipulation. The BC Cancer Agency treats some 4,000 men in B.C. with hormone withdrawal therapy each year - 60 per cent of all those who received a diagnosis of prostate cancer. The discovery of the new pathway could lead to far more effective treatments for these men.

There are 19,000 new patients diagnosed with prostate cancer a year in Canada - about 2,400 in B.C. The disease is the most prevalent cancer in men and, next to lung cancer, the most frequent cause of death.

The BC Cancer Agency provides a comprehensive cancer control program for the people of British Columbia. The Agency works closely 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 Research Centre conducts research into the causes and cures for cancer. The BC Cancer Foundation has a mandate to raise funds to support the work of the Agency and the Research Centre.

What we're doing about prostate cancer 

• BC Cancer Agency programs are interdisciplinary, involving radiation therapy, chemotherapy, hormonal treatment and brachytherapy. 
• The organization treats nearly 4,000 men each year with hormone withdrawal therapy. 
• Thirty-one per cent of the BC Cancer Agency's chemotherapy budget is devoted to the management of prostate cancer, approximately $6 million annually. 
• BCCA was the first organization west of Toronto to establish a program in prostate brachytherapy, which uses radioactive "seeds." 
• In addition to treating patients directly, the BC Cancer Agency has developed standards, guidelines and provincial cancer control policies for patient care and education all over B.C. 
• Collaborations between the BC Cancer Agency's scientists and clinicians have led to rapid translation of basic research and experimental studies into clinical trials and new treatments. 
• Many medical advances made in prostate cancer originated in the BC Cancer Agency's Cancer Endocrinology Department under the leadership of Dr. Nicholas Bruchovsky, including the new drug therapies combined low-dose DES and cyproterone acetate, neo-adjuvant hormonal ablation therapy and Intermittent Androgen Suppression. 
• In laboratories throughout the BC Cancer Research Centre, a critical mass of leading cancer experts are working to reveal the causes for prostate cancer and other cancers, and to develop new treatments. 
• The BC Cancer Agency uses population data from its BC Cancer Registry to determine appropriate cancer control strategies. 
• The Tumour Marker Laboratory has four components few organizations can offer for prostate cancer control: a databank; a serum bank; PSA testing; and research. Our efforts in genome science will help us establish a more strategic tumour tissue bank. 
• The BC Cancer Agency works with the Canadian Cancer Society (BC and Yukon Division) on initiatives to help patients cope, such as support groups, newsletters and public forums. 
• Our Cancer Information Centre provides information to patients, colleagues and the public.

For more information, please call Annabel Bruce
Ph: 604.877.6098 ext. 2076
Fax: 604.877.6146
Public Relations.