Grant: Operating Grant - Priority Announcement: INMD Start Up Funds (bridge funding)

Prostate cancer (PCa) is common amongst Canadian men. The Canadian Cancer Society estimates 25,500 men will be diagnosed with PCa this year, with 4,400 men succumbing to the disease. There is a geographical variation in the incidence of PCa with developed countries exhibiting substantially higher levels of the disease. This has been attributed, in part, to the "Westernized lifestyle" of high energy diets coupled with lack of physical activity and consequent development of obesity. Rising levels of obesity have been mirrored by a substantial increase in diagnoses of type 2 diabetes. Whilst it is unclear whether diabetes or obesity increases the risk of developing PCa, it is clear that obese patients with PCa experience worse prognosis. It is possible that this is due to the higher circulating levels of insulin in obese patients stimulating the growth of PCa cells. We have published results showing that diet-induced elevation of insulin stimulates the growth of PCa cells implanted onto mice. Treatment options for PCa vary, depending on the extent of disease at diagnosis. PCa cells require the male hormone, testosterone, for growth. Androgen ablation therapy involves the use of medications which reduce testosterone levels inhibiting PCa growth. This treatment is for both advanced disease as well as used in combination with curative treatments such as radiotherapy. Metformin is commonly used to treat diabetes. Recent studies show that metformin reduces various types of cancers in mouse models. Diabetics treated with metformin also experience lower levels of cancer diagnoses and/or prostate cancer related death. Ongoing work by our group is assessing the potential of metformin to prevent PCa development in mice. We will assess whether combining metformin with androgen ablation therapy can prevent PCa cell growth more than either treatment alone. We will also assess the benefit of combining metformin with radiotherapy.