Grant: Operating Grant

The Canadian Cancer Society estimates that 26,500 men will be diagnosed with prostate cancer (PCa) the disease this year, with 4,000 men succumbing to the disease. The incidence of PCa varies dramatically, with higher levels in developed countries. This is partly attributed to 'Westernized lifestyle' comprising of high energy diets with lack of physical activity, resulting in obesity. Increasing levels of obesity have been echoed by substantial increase in non-insulin dependent diabetes (NIDDM). Intrinsic radioresistance minimize insult of ionizing radiation and upregulates pro-survival pathways. We will determine if reduction in hyperinsulinemia can prevent radiation-mediated pro-survival IGF1 signalling, whereby metformin is acting as a radiosensitizer? Secondly, since hyperinsulinemia effect tumor progression, treatments which ameliorate insulin resistance may prevent progression to the hormone refractory state. A major problem that cancer patients face is the increased toxicity with chemotherapy using docetaxel. Hence, combining metformin with lower doses of docetaxel would be of high clinical relevance. After hormone blockage cancer stem cells is capable of regenerating the tumour population resulting in relapse. Hence it is important to eliminate frequently replicating tumor cells as well as abolish the slow dividing stem-like cells that are responsible for tumors regeneration. Consequently, successful elimination of CSCs may be an effective therapeutic strategy to be adopted in order to achieve complete remission from this disease. We hypothesize that metformin can sensitize cells and markedly improved the response of PCa cells to conventional radiotherapy and chemotherapeutic drugs by eradicating tumor cells as well as cancer stem cells (CSC) in the tumors. Our overall findings will support the fact that metformin may possess anti-cancer stem cell effects, which may contribute to its anticancer and chemosensitizing effect against prostate cancer.