Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Recurrence rates of cancer and the spread of cancer throughout the body through distant metastasis are two key determinants of cancer mortality, claiming a multitude of Albertans every year. A subpopulation of cells in tumors termed cancer stem cells (CSCs) are emerging as a significant factor in patient survival. These CSCs maintain a stem cell phenotype, much like embryonic stem cells (ESCs); and display the ability to adapt to a changing environment, which confers resistance to therapies, and the ability to re-establish the tumor post-treatment, leading to reduced patient survival. Despite its importance in patient survival, the mechanisms by which CSCs bypass regulation, acquire, and/or maintain stem cell like characteristics are not well understood. Using micro-environmental factors shown to promote CSC populations, my project aims to determine the similarities and the differences between the CSC and ESC response. This is done by growing various human cancer cell lines and embryonic stem cell line under hypoxia (low oxygen conditions) or Nodal (embryonic protein), both of which are involved in ESC maintenance and have been shown to increase CSC frequency. After the treatments, the cells will be harvested and the regulation present in ESCs will be compared to that of CSCs. Through this method, we can begin to highlight differences in how ESCs and CSCs respond to hypoxia and Nodal. The implications of these experiments will be two-fold: identifying the mechanism of dysregulation present in CSCs and determining potential targets for therapeutics. In order to completely eradicate cancer, cancer therapeutics must start targeting these CSCs in addition to the bulk of the tumor. Understanding the mechanisms by which it bypasses regulation is the first step in targeted therapeutic development. Therefore, this project has extensive consequences for therapeutic development and future cancer research that can vastly improve patient survival and quality of care.