Grant: CIHR - ICR / Cancer Research Society Partnership - Research Grants

Pancreatic cancer is a highly lethal disease with a dismal 5-year survival of 9%. Major limitations to improving the prognosis of pancreatic cancer have been the lack of its early diagnosis and efficient treatment options. Overcoming these limitations requires us to first gain precise and in-depth knowledge of pancreatic cancer, such as its establishment, invasiveness through metastasis and drug resistance. Facilitating tumor progression and metastasis is a process in which individual cells of primary tumor loose epithelial but acquire mesenchymal properties, referred to as "epithelial-to-mesenchymal transition (EMT)". The EMT process involves mosaic of cell states including the ‘stem-like’ state often associated with drug resistance and cancer recurrence. Yet, most of our current understanding of the EMT comes from bulk population measurements, which mask individual cell beahavior, thus undermining both the resolution and precision of our knowledge. In this project, we propose to address this by systematically studying the pancreatic cancer EMT at single-cell resolution. To this end, we will use an interdisciplinary approach by combining quantitative single-cell measurements, computational biology, biochemistry and cancer cell biology. Our single-cell study of EMT cell states, and their cell signalling and genome-wide gene-expression patterns will provide precise and deeper mechanistic understanding of pancreatic cancer, and will reveal novel biomarkers for its diagnosis.