Using PSA to target prostate cancer cells

One problem facing medical researchers working to find a cure for prostate cancer is how to kill cancerous cells while minimizing the damage to normal, healthy cells. Surgical techniques and radiation therapies have been refined to be as minimally invasive as possible.And various hormonal and emerging treatments target cancer cells by interfering with the way prostate cancer cells grow or interact with the body's immune system. Still, there is often collateral damage.

Then, Dr. Sam Denmeade of Johns Hopkins got the idea of using prostate-specific antigen (PSA), a protein made in abundance by prostate cancer cells, to produce a targeted therapy --- so prostate cancer becomes involved in its own destruction.He contacted Dr. Tom Buckley, then a University of Victoria biochemist and a world expert on genetically altering bacterial toxins so that they can be used in cancer therapy."Within two weeks," reports Denmeade, "he[Buckley] had generated the toxin, and then we tested it for toxicities against a variety of cancers in our lab before starting our studies in prostate cancer." An offspring of this research: PRX302.

PRX302, a drug developed by the Vancouver-based company Protox Therapeutics, uses prostate-specific antigen (PSA) to activate a series of steps leading to cell death. The drug is injected into the prostate, and its molecules bind to the surface of prostate cells. But the drug has been engineered to remain inactive until PSA removes its "activation tail." Then, it forms a structure that punches through a cell's membrane and causes cell death.



Because PSA is produced in high levels in men who have either prostate cancer or benign prostatic hyperplasia (BPH), therapies such as PRX302, which are activated by PSA, may prove effective in treating both conditions. In order to test the drug PRX302, Protox Therapeutics is collaborating with the Cancer Research Institute of Scott & White Hospital in Texas to run clinical trials.(Click on the adjacent picture to see a video about the first phase of the PRX302 clinical trial at Scott & White.)

The results of Phase I trials were reported earlier this year. The preliminary findings indicate that PRX302 is safe for and well tolerated by men with localized recurrent prostate cancer and by those who have BPH. The maximum-tolerated dosage was not reached in either the cancer or the BPH arm of this trial, however, so, although there were "convincing signs of biological activity," further trials are necessary to evaluate the drug's efficacy.

Initial findings were encouraging, though, and Phase II clinical trials are currently recruiting 1) men whose prostate cancer has recurred after they have completed treatment by external beam radiation therapy or radioactive seed implant and 2) men with moderate to severe BPH.

For more information:
The Scott & WhiteProtox Phase IIa Clinical Trial website
Protox Therapeutics News Releases