When Dr. Marianne Sadar made a career decision 12 years ago to "go after cancer," her greatest hope was that one day she'd make a breakthrough in the fight against the dreaded disease.
Yesterday, in her laboratory at the British Columbia Cancer Agency, Dr. Sadar explained how a research team she led has done just that -- coming up with a way to kill prostate cancer cells by using a "decoy molecule" that interrupts a key step in cancer growth.
The research could soon lead to the creation of a drug to treat patients at advanced stages of prostate cancer where no effective therapy is now available.
Prostate cancer, which afflicts one in seven men in Canada, or about 21,000 nationally this year, is easily treated if caught early. But if the cancer has moved to an advanced stage, the disease progression can only be slowed, not stopped, even when the prostate gland is surgically removed and aggressive radiation treatment is used.
The growth of prostate tumours is initially fuelled by testosterone, an androgen. In advanced cases, however, the tumour, for unknown reasons, continues to grow even without the presence of androgen. This is known as the androgen-independent stage, and once patients are at that level they usually have only a few years to live.
Dr. Sadar's research was aimed at finding out how the cancer grows without androgen. In the process, the researchers identified a key role played by androgen receptors, which are activated by an agent that scientists haven't yet identified.
Even without knowing what that mysterious agent is, Dr. Sadar's team was able to create "decoy molecules" that can be used to overwhelm the process that triggers the androgen reception.
"We've been the first ones to do this. We've created the decoys. We've showed that it works, that you can really keep the tumours in check," Dr. Sadar said.
The androgen receptor decoy molecules block the growth of prostate cancer cells so effectively that tumours don't just stop growing, they begin to shrink.
"It causes them to die. It kills them," Dr. Sadar said, as she flashed a slide on her computer screen that showed cancer cells dying after the decoy molecules were introduced to a test sample.
"You can see that our decoys reduced the number of cells that are dividing. This is a picture showing, anything really bright green like this is a cell that is dying, so you can see in our control . . . there's not many cells that are dying," Dr. Sadar said, showing a photograph with a scattering of green cells.
"But when we have our decoy there are a lot of cells dying . . . just an enormous number dying," she said, with the next slide showing a profusion of bright green cells.
In a paper, just published in the Proceedings of the National Academy of Sciences, the researchers state that the use of the decoy molecules caused a tenfold decrease in prostate-specific antigen, or PSA levels, and reduced the size of tumours fourfold.
Dr. Sadar, who worked on the project with Steven Quayle, Nasrin Mawji and Jun Wang, said the first promising results came four years ago when they managed to kill prostate cancer cells in a lab test.
"We showed it in a [human]tissue culture dish. And that was incredibly exciting, then we had to go, 'Well, what you see in a dish doesn't mean it would work when a tumour is growing in an animal.' It took us four years to do all the animal studies, to create all the delivery systems, to make sure that the decoy is being made properly."
Dr. Sadar said the tests showed the process works just as well in lab mice as it does in a culture dish.
"It's amazing. We've been working on this for eight years and we've identified this vulnerable spot [on the androgen receptor]. . . and because we have this new target, we can now create drugs that work instead of this decoy. So that's where we're going now. It's very exciting."
Moving research results out of lab and onto drugstore shelves can take decades -- and often what works on mice doesn't prove to be effective on humans.
But Dr. Sadar said the researchers are confident that their findings will quickly lead to a human drug that, while it might initially be used to treat advanced prostate cancer patients, might eventually be developed for use at earlier stages, to avoid prostate surgery.
"I don't think we're years and years away from it," she said of the creation of a drug. "Now that the paper has just come out there will certainly be pharmaceutical companies that will be jumping on this. I believe this is a paper, or work, that will cascade, to have very rapid screening against this therapeutic target," she said.
"I hope that our work will be the pivotal point that leads to a drug being discovered. It would be nice if it's still us [in the lead] but now it's out there for the whole world to use. I want the research to move quickly now, so that someone, if it's not us, finds that drug."
Mark Hume