Grant: CIHR Fellowship

Breast cancer is the most common type of cancer in women and the second leading cause of cancer related mortality. Approximately 1-in-8 women will be diagnosed with breast cancer in their lifetime. Advances in breast cancer research have identified three tumor characteristics that can be used by physicians to choose appropriate therapy for targeting the cancer. However, some breast cancers are "triple negative" and lack these characteristics, causing them to be more difficult to treat. Triple negative breast cancer (TNBC) accounts for 12% of breast cancer diagnosis and these patients have the highest mortality of all breast cancer patients. TNBCs are typically treated with cyclophosphamide, anthracyclines, and taxane therapy since there are currently no specific markers to target therapy. Therefore, tumors in these patients have a high rate of drug resistance. Thus, there is a need for the discovery of new biomarkers that can be used to personalize TNBC treatment and detect drug resistance, thereby increasing patient survival. The objective of this project is to identify biomarkers that detect drug effectiveness and resistance using metabolites found in TNBC patient derived tumor xenografts (PDTX). Unlike the gene mutations that cause cancer, metabolites can be released from cancer cells and measured in blood and urine. We hypothesize that tumor, plasma and urine metabolite biomarkers can be used to predict and detect drug sensitivity and resistance in TNBCs. Metabolite changes can also occur in response to drug treatment. Furthermore, metabolism can be altered in TNBCs that are sensitive and resistant to drug therapy. Therefore, identifying metabolite biomarkers of drug sensitivity and resistance prior to treating patients may allow physicians to choose more effective treatment. Moreover, early detection and rapid intervention may be possible through measuring metabolite biomarkers in plasma and urine during drug therapy.