The James Buchanan Brady Urological Institute
 
           A PUBLICATION OF THE PATRICK C . WALSH PROSTATE CANCER RESEARCH FUND
 
Volume VIII, Winter 2012
A Faster Way to Find New Drugs for Prostate Cancer: Taking a Close Look at What's Already Out There

Remember the TV show, MacGyver? The main character was a genius at using everyday items to get out of a tight spot. The beauty of his approach was a creative reworking of the materials at hand. Epidemiologist Elizabeth Platz, Sc.D., oncologist Srinivasan Yegnasubramanian, M.D., Ph.D., and colleagues are thinking along those same lines, for a lot of good reasons.

One of them is time. To anyone who could benefit from a better medical treatment than the ones currently out there, it takes an inordinate amount of time for the drug pipeline to do its job. From the time a scientist develops an agent, tests it in the laboratory (in tissue samples, Petri dishes, animal models and any other preclinical tests), gets approval from the government for clinical testing — first, to make sure it is safe and follows the fi rst rule of the Hippocratic oath, which is, “Do No Harm,” then to see if it helps, and if so, at what dose — it can take years.

It can also take a whole lot of money. Drug development is “exorbitant,” say Platz and Yegnasubramanian, and the cost to bring just one drug through this process, from the laboratory to receiving regulatory approval, is estimated to top $1 billion.

One way to streamline this process is to look at the drugs that are already out there, sitting on the shelves in local pharmacies — drugs whose means of action and potential side effects are already known. “Rapid laboratory screening of these drugs, followed by focusing on the strengths of existing, well-characterized studies could, with relatively little expense, expedite our ability to identify and test drugs for new uses in clinical trials,” says Platz.

How much does it cost to
bring just one drug through
the pipeline, from laboratory
development to the pharmacy
shelves? $1 billion.

With the goal of finding drugs approved for other diseases that might help treat prostate cancer, Platz, Yegnasubramanian, and a transdisciplinary team used a novel laboratory- epidemiology approach. Their results were published in Cancer Discovery. “It was a two-step program,” she says. “First, we did in vitro screening, to see if drugs inhibited the growth of prostate cancer cells.” They looked at 3,187 different compounds. “Then, we looked at the link between the most promising drug and the risk of prostate cancer in a large study with long-term follow-up.” The result: What the scientists, and colleagues Jun Liu, Curtis Chong, Joong Sup Shim, Stacey Kenfi eld, Meir Stampfer, Walter Willett, Edward Giovannucci, and Bill Nelson, believe is “compelling evidence” that a drug commonly used to treat heart problems, digoxin, should be considered as a potential drug for prostate cancer.

The team’s testing ground in humans was the massive, Harvard-led Health Professionals Follow-up Study, which follows thousands of people for decades, notes which medicines they take, and, among many other functions, documents any illnesses they develop. “Digoxin was highly potent in inhibiting prostate cancer cell growth in the laboratory,” says Platz, “and the men who regularly took this drug had a 25 percent lower risk of prostate cancer than other men.” Men who took digoxin for a decade or more had the lowest risk. The results offer exciting potential for a new drug to help reduce a man’s risk of developing this disease. “Perhaps of equal importance, our study illustrates the power of the transdisciplinary approach in translational cancer research,” notes Platz.

 
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