Grant: Doctoral: Vanier Canada Graduate Scholarships

Breast cancer is the most common malignancy in Canadian women and about a third of women will develop metastases and die, despite treatment by both surgery and chemotherapy. This is explained in two ways. First, cancer cells spread (metastasize) to other organs and establish secondary tumors. Second, the ability to treat patients and kill cancer cells with chemotherapeutic agents is compromised by the development of resistance to these agents through the activation of cell survival signals by bioactive signaling molecules. Hence, there is an urgent need to identify the signal pathways that lead to these problems. Such molecules are known to be degraded by a group of three lipid mediators called lipid phosphate phosphatases (LPPs). It has been hypothesized that abnormal expression levels of LPPs make cancer cells hypersensitive to the signal effects of bioactive signaling molecules, promoting tumor growth. However, the relative function of the three LPPs in attenuating cancer cell survival signaling is poorly understood. To study these roles, I will alter LPP activity in breast cancer cell lines to determine how these changes modify the activation of cell survival signals that are normally upregulated in cancer cells and the ability to kill the cancer cells upon treatment of common chemotherapeutic drugs. Overall, this knowledge should help to develop new strategies and treatments for improving the effectiveness of surgery and chemotherapy, particularly for cancers that show resistance to conventional treatment regiments. These developments should lead to increased survival rates and cures for cancer patients.