Grant: Master's Award: Canada Graduate Scholarships

Cells are constantly faced with changes in nutrient levels. Unless cells can overcome these shortages, death may result. How do cells cope with nutrient limitations to promote cell survival and growth? One survival adaptation is called autophagy, which refers to the breakdown of fats, proteins and other dispensable contents of the cells. The breakdown products are recycled to generate energy required for survival. Autophagy is of great interest to cancer because the geometry of solid tumors results in them being characteristically nutrient poor. Moreover, chemotherapies can induce autophagy. Thus, tumors use autophagy to evade death associated with these stresses, and promote survival of indolent cells which may cause tumor relapse. We predict that low nutrient levels and/or chemotherapy cause tumors to survive by autophagy and this contributes to tumor reoccurrence. Therefore, it is a logical hypothesis that blocking autophagy can prevent relapse. However, there have been limited studies examining autophagy in human tumors. To test our idea, we will utilize an established ovarian cancer bank at the BC Cancer Agency. This resource has collected tumor samples at the time of diagnosis, after surgery/chemotherapy, and at the time of reoccurrence. Using this unique resource we will ask three questions: 1) Does autophagy impact overall tumor-free survival? We will correlate levels of tumor autophagy markers with patient survival. 2) Does autophagy predict treatment responses? We will determine if increased autophagy at the time of diagnosis and/or treatment affects treatment response. 3) Is autophagy a regulator of tumor progression? We will inhibit autophagy in both human and mouse models of ovarian cancer to assess its role in tumor progression. Together, our study will provide critical insight into how autophagy functions during cancer and provide preclinical data to support the coupling of autophagic inhibitors with standard anti-cancer treatment.