Grant: Doctoral: Vanier Canada Graduate Scholarships

Renal Cell Carcinoma (RCC) affects 1/56 Canadians and has a dismal prognosis; only 10% of patients with metastatic RCC survive 5 years. Current regimes increase survival only by months and cost up to $50,000/year. No two patients have identical tumors and this heterogeneity compromises our efforts to treat RCC. A fresh look at RCC biology is needed, as well as a "customized approach" offering personalized treatment in order to have the highest chance of responding. Most tumors use more sugar and less oxygen than healthy tissues. This leads to several advantages that help cancer spread. Cancer's oxygen independence is based on shutting off their energy-producing units called mitochondria. Multiple cancers are characterized by "shut off" mitochondria and there is evidence that turning them back on may be effective. Since mitochondrial suppression is not found in normal cells, therapies that normalize mitochondria in cancer do not affect normal cells, unlike standard chemotherapy. Dichloroacetate (DCA) is an inexpensive drug that activates mitochondria and shows positive results in animals with cancer and patients with brain cancer. We have evidence that DCA activates mitochondria and decreases cancer growth in RCC without effecting healthy kidney cells. Our plan is to take the next step, testing the effects of DCA on tumors in animal models as well as on tumor samples (in the test tube) taken from our patients during surgery. This will lead to testing DCA in actual patients. While 2/3 of patients with RCC have suppressed mitochondria, this is not the case with all. We will study the tumors at the time of biopsy to determine which tumors have suppressed mitochondria and respond to DCA. We will then only treat these patients with DCA, increasing the likelihood of having a good result with less adverse effect; while the other patients will receive a standard RCC treatment. Thus we can tailor therapy uniquely for each patient - a process known as personalized medicine.