Grant: Doctoral: Vanier Canada Graduate Scholarships

Lung cancer is the number one cause of cancer death worldwide. High mortality rates are attributed to poor therapeutic strategies and a lack of screening for early detection. Two subtypes of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SqCC) account for more than 70% of all lung cancer cases. These subtypes differ in their location within the lung, cell type composing the tumor and importantly, in their response to therapies, suggesting they may develop from distinct molecular alterations. However, subtype specific aberrations and the biological pathways they deregulate remain largely unknown. As such, AC and SqCC tumours are treated primarily as a single disease, likely contributing to the poor prognosis and therapeutic responses typically observed in lung cancer. The goal of my research is to address the hypothesis that lung AC and SqCC develop through distinct genetic alterations, and that these differences contribute to subtype specific development. My aim is to identify causal subtype specific alterations and distinguish the molecular pathways they regulate. To accomplish this, I will use an integrative approach to assess multiple levels of DNA and gene expression disruption in a panel of lung cancer specimens. Only DNA alterations causing gene expression changes will be further examined as these are most likely to promote lung cancer development by disrupting cell signaling pathways. Comparison of alterations identified in AC and SqCC via this approach, will likely reveal causal subtype specific alterations as well as shared and uniquely altered pathways. If my hypothesis is correct, my findings could identify diagnostic markers for early detection, and new subtype specific therapeutic targets. This work will directly improve the health of Canadians by providing evidence to change the way lung cancer patients are classified and treated, which will improve the poor prognosis and survival associated with lung cancer.