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

Lung cancer is the leading cause of cancer death worldwide. This is largely due to the typical late stage of diagnosis and a lack of effective treatment options. The ability to predict which drugs will be most effective for individual lung cancer patients would greatly improve overall survival. This study aims to identify such predictive biomarkers by investigating the hypotheses that short RNA molecules called microRNAs (miRNAs) are deregulated in accordance with drug resistance and sensitivity, and therefore can be used to predict treatment outcome. miRNAs are major regulators of gene expression, and have a well established role in a variety of cancer types including lung cancer, although the role of miRNAs in lung cancer drug response is largely unknown. By comparing cases that responded and did not respond to specific drugs, this study aims to identify miRNAs that are associated with drug resistance and sensitivity. Further, this study aims to identify which genes and biochemical pathways are regulated by these resistance- and sensitivity-associated miRNAs to gain knowledge about the mechanisms of drug response. The pathways identified here could be targeted to improve drug response; therefore, the final aim of this study is to use this knowledge of drug response-associated miRNA pathway regulation in order to design new, more effective drug regimens. Ideally, existing FDA approved drugs will be used in combination with the drug of interest to improve treatment response. This work will directly impact the health of Canadians by identifying novel predictors of drug response to direct current treatment options to those most likely to respond. It will also generate much needed insight into the biology governing drug response that may be used for the development of new drug combinations to improve treatment efficacy and patient survival.