BC Cancer Agency researchers will receive more than $1 million Canadian from the US Department of Defense Prostate Cancer Research Program to test two innovative ideas that may one day lead to potent therapies in the battle against prostate cancer.

Researchers have been stymied in predicting which prostate cancer drugs will have the best therapeutic efficacy because initial success in animal models doesn't always translate into success in human trials. The first grant for $500,000 awarded to Drs. YZ Wang and Peter W. Gout will be used to study a xenograft model developed by Dr. Wang, which allows the growth of freshly isolated human prostate cancer tissue in mice.

In 2001, Dr. Wang was the first in the world to successfully graft both early-stage and advanced human prostate cancer specimens in mice, and has since perfected the technique with a more than 95 percent success rate. Before Dr. Wang's achievement, scientists had been able to grow patients' prostate cancer tissue in mice, but only sporadically and only when the malignancies were highly advanced.

This new xenograft model is exciting because it may be used a) as a prognostic tool, to determine which cancers are likely to progress to an advanced stage; b) to test the effectiveness of new drugs with confidence that they may be useful in the clinic, and c) to select the best drugs for individual patients.

"We're looking ahead to a new era of personalized cancer therapy," says Dr. Wang. "Right now we don't really know if a patient's cancer is going to respond better to drug A, B or C. But imagine being able to take a particular patient's tumour tissue, transplant it to several mice, and then test the effectiveness of different drugs on the patient's tumour.

"In the future, the hope is that we'll be able to tell which drug is going to have the maximum benefit for a patient right away, rather than a patient trying one drug after another."

Using the xenograft model, Dr. Wang's colleague, Dr. Peter W. Gout, will test an existing anti-arthritis drug, sulfasalazine, which in preliminary laboratory tests has proven itself as a powerful agent in blocking the uptake of cystine (an amino acid) in cells, a process essential for the growth of some cancers. In the late 1990's, Dr. Gout discovered that certain cancer cells can be starved to death by preventing the uptake of this particular amino acid.

"We found in a pilot study that sulfasalazine caused a 60 to 80 percent reduction in the growth of transplanted prostate tumours in mice, with no major side-effects," says Dr. Gout. "We will be testing the efficacy of sulfasalazine as a single agent in treatment of early and late stage tumours, and in combination with other conventional drugs.

"If sulfasalazine proves effective, we could test it almost immediately in human clinical trials since it has been used for decades in the treatment of inflammatory diseases."

The second research study to be funded is being conducted by Dr. Marianne Sadar, and is based on pioneering work conducted in Dr. Sadar's lab in 1999. Scientists have known for some time that the action of the male sex hormone on prostate cancer cells is mediated by an androgen-receptor, a protein that is switched on when it binds to testosterone. The activation of this protein is crucial in the growth of prostate cancer cells. Withdrawal of testosterone prevents activation of the protein and is the basis of hormone therapy treatment. However, in some cases, androgen-independence occurs, whereby the prostate cancer cells grow out of control, without the presence of testosterone.

Sadar discovered a possible pathway on the androgen-receptor through which prostate cancer cells switch on the activation of the protein, even without testosterone.

In the $530,000 Department of Defense funded preclinical trial, Sadar will test a new molecule engineered in the lab, which contains multiple copies of the region on the androgen-receptor believed to be the pathway through which prostate cell growth is reactivated.

"The molecules act as decoys, effectively blocking the unknown agent from binding to the region of the androgen-receptor at risk. Instead the agent is fooled into binding onto the chemically engineered decoys," says Dr. Sadar.

"Essentially, the molecules mop up any agents that could bind to the vulnerable area of the androgen-receptor to turn on prostate cancer cell growth."

Dr. Sadar's study will determine the best timing for delivery of the agent, and monitor the effect of systemic treatment on other tissues and organs.

One out of eight men will develop prostate cancer in his lifetime, primarily after the age of 70. In B.C. an estimated 3,100 men will diagnosed with prostate cancer and 540 will die from the disease this year.

The BC Cancer Agency, a part 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 Research Centre conducts research into the causes and cures for cancer.

For more information, please contact:

Papinder Rehncy

BC Cancer Agency Public Relations

Tel: (604) 877-6000, extension 2378