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Target: The Big C Vice President Research, Office of the Nov 30, 2007

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November 2007 7 K c y m Docket no.: 1203 Version no: 2 client : UBc Research Date: 2007 Oct 12 Item: Frontier magazine Size: 8.5x11.75 inches Logos: repro Photos: hires Line Screen: 150 line Fonts: DIN, A Garamond Pro, Berthhold Akzidenz Grotesk, Helvetica Neue Proofed by:ROS/KB/SD All trapping is the responsibility of the printer/ pre-press company outputting final film/plates. At tHe forefroNt of trANSlAtIoNAl reSeArCH, MArtIN GleAve AND tHe ProStAte CeNtre Are ACCelerAtING DISCovery IN CANCer reSeArCH wHIle BrINGING tHerAPeUtICS to PAtIeNtS More qUICkly AND effICIeNtly The year was 1966 and scientific discoveries in the lab were reaching an unprecedented height – from the first synthesis of insulin in China to the deciphering of the DNA code by an MIT biochemist to the approval of the human use of “the Pill” by the Food and Drug Administration. It was also the year that Canadian-born urologist Dr. Charles Huggins was recognized for his discovery that some cancer cells, like normal body cells, are dependent on hormonal signals to survive and grow and that by depriving cancer cells of the correct signals, the growth of the tumours could be slowed down, at least temporarily. This seminal find won Huggins the 1966 Nobel Prize for Physiology or Medicine and revolutionized modern oncology by proving that some cancers could be controlled by purely chemical means. It also left a lasting legacy in Canadian prostate cancer research that prompted many Canadian urologists to further push research to new heights of discovery – without leaving the country. Dr. Martin Gleave, UBC Vancouver Professor of Urologic Sciences and Director of the Prostate Centre at Vancouver General Hospital (VGH), counts himself as one of those urologists. “In Canada, we have a great network of uro-oncologists that really allows us to function as a team in various clinical trial networks,” says Gleave. “It also allows Canada to hit above its weight globally in prostate cancer research.” Through the Prostate Centre at VGH, Gleave, co-Directors Dr. Larry Goldenberg, Dr. Paul Rennie and their team have helped position Vancouver (and UBC) as a major hub for prostate cancer research not only in Canada but also all over the world. Now in its seventh year of operation, the centre is internationally recognized as one of the leading facilities in the research and treatment of prostate cancer. The centre’s primary focus is to understand the molecular mechanisms that underlie cancer progression and the development of treatment resistance. In order to discover new ways to inhibit the spread of the disease, Gleave and his research team investigate how cancer cells change when stressed with treatment and then study the gene that produces that particular change to determine whether cancer cells need it for growth or survival. “When we try to go in and kill cancer cells, like any living Target: The Big C K c y m Docket no.: 1203 Version no: 2 client : UBc Research Date: 2007 Oct 12 Item: Frontier magazine Size: 8.5x11.75 inches Logos: repro Photos: hires Line Screen: 150 line Fonts: DIN, A Garamond Pro, Berthhold Akzidenz Grotesk, Helvetica Neue Proofed by:ROS/KB/SD All trapping is the responsibility of the printer/ pre-press company outputting final film/plates. November 2007 November 2007  organism, they respond by wanting to survive. So cancer cells turn on genes that help them survive our systemic anti-cancer therapies,” says Gleave. “Through this, we’re interested in understanding what genes these cancer cells are turning on for survival and then developing inhibitors to block those survival pathways.” The research has resulted in the successful characterization of the role of several cancer survival genes such as bci-2, clusterin, HSP 27 and IGF binding proteins. Although the centre does not patent these genes, it patents the use of these genes through therapeutic inhibitors. One such inhibitor, OGX-011, is now the leading drug candidate for OncoGenex, the Vancouver-based biotech firm that Gleave founded in 2000 to patent intellectual property developed at the centre. OGX-011, which targets and inhibits the survival gene clusterin to enhance cancer cell death after chemotherapy, is currently in Phase Two clinical trials across North America and is poised to move onto registration Phase Three trials beginning in 2008. A second drug, OGX-427, which targets the survival gene HSP 27, has recently moved into its first in-man trials. In addition to his role as Director of the Prostate Centre, Gleave is Chief Scientific Officer of OncoGenex, which now has five patented products that have been out-licensed, three of which are currently moving through clinical development. The infrastructure at the Prostate Centre has helped to accelerate discovery and bring new therapeutics to patients more quickly and efficiently. It is this translational approach to research – where discoveries in the lab are directly translated to therapeutic developments – that has distinguished the centre from other cancer research institutes at other universities. Gleave also points to the multifaceted collaborations across disciplines and the involvement of research hospitals, academic institutions and industry, like local biotechs, Angiotech, QLT, Kinexus and major pharmaceutical companies like Aventis, Eli Lily and AstraZeneca in addition to IBM, that have helped shape the centre’s noteworthy achievements. “Part of our success is that we function as a translational cancer research program where we are intent on doing high- quality discovery research but that research is a means to an end,” says Gleave. “We want to use the research to develop products to improve the outcome of patients with prostate cancer and in doing so function as a hybrid, between an academic centre and an industry, to commercialize products and enhance Canada’s economic competitiveness in the emerging biotech centres around the world.” Not only has the centre attracted national and international dollars into the province and provided a framework to discover, develop and out-license products to biotech firms like OncoGenex but it has also attracted key personnel with expertise in the industry. This level of expertise has helped BC grow the critical infrastructure necessary to be competitive in technology transfer at the academic level. The results speak for themselves: UBC is now ranked number eight in the world and number one in Canada in technology transfer due in large part to successes like the Prostate Centre and OncoGenex. For patients currently suffering from cancer, the advantage of having this type of centre locally is more direct. By having the capacity to attract the best and brightest clinicians and researchers, patients benefit from gaining access to novel treatments that normally would have only been available at clinics elsewhere in the world. For Gleave, it is this improvement in patient treatment that ultimately drives him and his colleagues towards further discovery: “One of my dreams would be to take a discovery like we have with clusterin and HSP 27 and design and develop an inhibitor that then goes all the way to market and becomes something that prolongs life. That’s the holy grail of translational research,” he says. “When you’re dealing with advanced or recurrent cancer, people can no longer be helped by surgery and it’s too complicated to believe there is only one magic bullet. So we have to come up with multiple different target therapies to control the disease and delay progression, turn the cancer into a chronic disease that people die with rather than of.” Dr. Martin Gleave is a UBC Professor of Urologic Sciences and Director of the Prostate Centre at Vancouver General Hospital (VGH). The centre has received funding from the Canada Foundation for Innovation (CFI), the Terry Fox Foundation, the National Cancer Institute of Canada (NCIC), the BC provincial government as well as numerous private funders. “wHeN yoU’re DeAlING wItH ADvANCeD or reCUrreNt CANCer, we HAve to CoMe UP wItH MUltIPle DIffereNt tArGet tHerAPIeS to tUrN tHe CANCer INto A CHroNIC DISeASe tHAt PeoPle DIe wItH rAtHer tHAN of.” Photo> Brian Hawkes


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