Grant: CIHR Fellowship

Cancer is the leading cause of death in Canada. Canadian Cancer Statistics estimates that 2 in 5 Canadians will be diagnosed with cancer in their lifetime. Worldwide, 67% of cancer deaths in patients occur due to metastasis, the spread of cancer from its place of origin to other organs. Many biological processes underlie metastasis, one of the most important being "epithelial-to-mesenchymal transition" or EMT. During this process, a different set of genes are expressed in cancer cells which allows them to break away from the original tumor, circulate in the body, and establish new tumors in different parts of the body. In this study, I propose to examine the role of a protein known as ATR kinase in EMT. My preliminary data suggests that ATR prevents DNA damage in cancer cells during EMT, thereby allowing cancer cells to survive. Excessive DNA damage can kill cancer cells; thus, targeting ATR to induce DNA damage may be a viable strategy to stop EMT and metastasis. Several companies have created inhibitors of ATR, but they have not been tested in their ability to stop metastasis. I will use these inhibitors and cutting-edge mechanistic and DNA/RNA sequencing technologies to uncover novel mechanisms of ATR in EMT. Furthermore, using cancer cell lines and preclinical animal models, I will test the efficacy of ATR inhibitors on suppressing EMT and metastasis. 233,900 new cancer cases and 85,100 cancer deaths are expected in Canada in 2022. Unveiling these fundamental biological mechanisms will bring us one step closer to filling in the current gaps in knowledge in the fields of cancer genetics and cell and molecular biology. Findings from this study will open up new avenues of cancer research for scientists across Canada and worldwide. More importantly, the translational implications of my project are significant as they have the potential to reduce cancer mortality and improve the quality of life of cancer patients in Canada and around the world.