Sherbrooke, November 16, 2017 – Prostate cancer, the most common cancer in men, affects one out of seven Canadian men. Professor Robert Day and his team have just discovered a major biochemical mechanism that could hold the key to the disease’s progression. The breakthrough, published in Cancer Research, appears so promising that the team is already beginning to work on diagnostic and therapeutic applications.
The group at the Faculty of Medicine and Health Sciences (FMSS) had already identified the PACE4 enzyme, a protein that is overexpressed in certain individuals. Inhibition of the PACE4 protein blocks the progression of prostate cancer. Nevertheless, the protein’s mechanism of action has remained poorly understood…at least until now.
Professor Robert Day (research professor in the FMSS’s Department of Surgery, Division of Urology, and at Centre de recherche clinique du CHUS) and his team have made a completely unexpected discovery. They found that the PACE4 enzyme, in fact, has a small twin in an alternative form. This isoform protein, referred to as alternative PACE4, is produced as the result of PACE4 undergoing internal transformation. Unlike PACE4, which is found in all body cells, alternative PACE4 only occurs in cancer cells.
“All our research efforts were focused on the PACE4 protein in prostate cancer, so finding an alternative form was quite a surprise,” revealed Day. “This chance discovery has proven very significant because we now know that it’s the alternative form that plays an important role in the progression of cancer cells.” Alternative PACE4 is also found in other cancers such as the thyroid, pancreatic, and lung cancer.
Biochemistry doctoral student Frédéric Couture—a member of the research team and first author of the article published in Cancer Research—was also amazed by this breakthrough. Couture pointed out that “the discovery will led to the development of optimal therapeutic targets, which is a considerable source of hope for prostate-cancer patients. It also opens the way for new avenues in terms of diagnosis and more personalized treatment. There is reason to have high hopes for the future!”
This research—primarily funded by the Movember Foundation and Prostate Cancer Canada—wouldn’t have come about without the valuable collaboration of surgeon and urologist Robert Sabbagh. Research professor in the FMSS and at the Centre de recherche clinique du CHUS, Sabbagh manages and operates on many prostate-cancer patients in addition to heading up several research projects on the topic. Sabbagh, an active contributor to the biobank and database for cancer research, has worked with Day from the outset of his research. This coalescence of scientific and clinical expertise produces an incomparable perspective of the reality of patients and research.
« We at Prostate Cancer Canada along with our men’s health partner The Movember Foundation are delighted with the incredible work being done by Dr. Day and his team,” said Dr. Stuart Edmonds, Vice President of Research, Health Promotion and Survivorship at Prostate Cancer Canada. “This publication, in a prestigious journal no less, signifies a significant stride forward in our collective efforts to identify therapeutic targets to not only treat men with advanced prostate cancer, but cancer more generally. On behalf of the 1 in 7 Canadian men who will develop prostate cancer and their families, thank you to the generous Canadians whose participation in Movember and ongoing charitable giving makes ground-breaking research such as this possible. »
“The way I see it,” stated Day, “the discovery of alternative PACE4 and its role in prostate cancer are major breakthroughs. The next steps are critical in effectively neutralizing this protein, which is essential to tumor progression. We are on the right track!”
This research conducted by Day and Sabbagh also receives support from the Canadian Cancer Society and La Fondation Mon Étoile for cancer research.
Prostate cancer is the most common cancer to affect Canadian men, with one in seven diagnosed with the disease in their lifetime. The scientific community foresees the proportion increasing to one in four in several years. Prostate cancer can be slow-growing; some men who develop prostate cancer may live many years without ever having it detected. Age is the more important risk factor: risk increases starting at age 50; most cases are diagnosed in men over 65. Family history, overweight, and poorly balanced diet also rank among the conditions that increase the risk of prostate cancer.
*Press release courtesy of l’ Université de Sherbrooke