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Discoverers' recompense

July 18, 2013

By Alisa Kim

Three Sunnybrook Research Institute (SRI) scientists won Movember Discovery Grants from Prostate Cancer Canada.

The awards are worth $200,000 over two years and support promising new directions in prostate cancer research. Prostate Cancer Canada approved 40 of the 154 applications submitted, for a total investment of $7.7 million.

Dr. Stanley Liu, a scientist in Biological Sciences at SRI, scored funding for his research, which looks at how microRNAs (short sequences of ribonucleic acid) help prostate cancer cells evade death from radiation, a main treatment for prostate cancer.

"Our goal is to try and make radiation work better in patients. One of the ways we're trying to do that is by figuring out how certain prostate cancer cells are able to survive radiation. If we're able to figure out the wiring and the pathways that govern resistance to radiation, we'll be able to target those pathways," says Liu, who is also a radiation oncologist at Sunnybrook's Odette Cancer Centre.

Discovered in 1993, scientists now know that microRNAs regulate which genes are expressed and when. They do this by attaching themselves to messenger RNAs and preventing them from being translated into proteins. More than 700 microRNAs have been identified in people, and several hundreds more are thought to exist. MicroRNAs govern the expression of about 60% of all human genes and can suppress hundreds of targets each.

"They put the brakes on protein expression," says Liu, who is also an assistant professor at the University of Toronto. "If you put the brakes on a tumour suppressor, then that microRNA can be oncogenic and make a cancer cell more aggressive. On the other hand, if a microRNA targets components involved in repairing DNA, then those cancer cells might be more sensitive to treatment—if the cells can't repair their DNA as well."

Growth in the field of microRNA research has been "exponential," with hundreds of scientific papers published on the topic each month, says Liu. He notes that radiation-induced changes to microRNAs in cancer cells are well documented, but which of the hundreds of microRNAs are the main players in radiation resistance, and the precise mechanisms by which resistance occurs, remains unknown.

"If you give radiation to patients, microRNAs change within minutes to hours. We can say things are changing—some [researchers] have reported profiles: 'This is going up, this is going down,'—but no one's said, 'This is one that is actually involved in response to radiation and making cells resistant.' How does that microRNA actually do that? That's a critical area that hasn't been addressed. That's what we're trying to do," says Liu.

In addition to uncovering the biological mechanisms behind treatment resistance, Liu also hopes to unveil the predictive power of microRNAs, which can be detected in blood, urine and saliva, so that doctors can tailor therapies according to severity of disease. "They're very stable. They can be used as biomarkers, not just in detection of cancer, but also in prognostication—which patients might have an aggressive cancer and might [therefore] need aggressive treatment. It's still in relative infancy, but those are questions we're also interested in."

Two other SRI scientists succeeded in their bid for a Movember Discovery Grant. Dr. Charles Cunningham, a senior scientist in Physical Sciences at SRI, gained funding for his research on hyperpolarized carbon-13 imaging of advanced metastatic prostate cancer. Dr. Greg Czarnota, director of the Odette Cancer Research Program at SRI, secured funding for his research on the use of microbubbles to enhance radiotherapy for prostate cancer.

Dr. Stanley Liu