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

Breast cancer is a major worldwide public health problem. An astonishing 22,900 new cases of breast cancer and 5,400 disease related deaths are projected for 2009 in Canada. This makes breast cancer one of the most common malignancies in Western women. To date, research has focused primarily on targeting late stage cancers to slow their progression. Despite the emergence of new generation therapeutics success has been limited and mortality remains high for individuals with advanced cancers. To ultimately prevent the onset of aggressive cancer we need to expose and target the earliest events that drive normal cells into cancerous cells. This approach will not only drastically improve patients quality of life but also decrease the financial burden on the health care system. YB-1 is an oncogene (cancer causing gene) that when expressed in mice leads to tumour development. Our lab has engineered a system that recapitulates this mouse model to study the consequences of activating YB-1 in normal human breast cells. This gives us insight into the role of YB-1 during early malignant transformation. For the first time ever, we have demonstrated that YB-1 promotes genomic instability. Normally, a tightly regulated mechanism ensures the integrity of a cells genome (DNA) by preventing errors from occurring when it is copied during cell division. Our preliminary data suggests that YB-1 hijacks this process allowing for abnormalities that promote the activation of oncogenes to fuel cancer progression. My research is truly bench to bedside. I will begin by investigating how YB-1-mediated genomic instability arises and subsequently enhances cancer progression. In turn, I will screen off-patent compounds to evaluate their ability to prevent, and even reverse, genomic instability. I envision that one day drugs identified in this study will be used in the clinic to stop cancer progression at the earliest stages thus curbing the emergence of aggressive, drug resistant cancers.