I am currently an associate professor in the Department of Surgery at the University of Toronto, a surgical oncologist at the Toronto General Hospital, a scientist at the Princess Margaret Cancer Center, and a Canada Research Chair in translational colorectal cancer research.  I obtained my MD from Queen’s University and completed a General Surgery residency at the University of Western Ontario. I subsequently went on to complete a fellowship in surgical oncology at the University of Toronto, specializing in gastrointestinal malignancies. During my fellowship I completed a PhD at the University of Toronto studying cancer stem cells in colorectal cancer (CRC). I also established a viable tissue CRC tumour bank that includes over 300 patient derived samples. The xenograft bank is complemented by organoid cultures, and an increasing bank of normal intestinal cultures.

Despite being one of the best understood cancers from a genetic perspective this has not translated into a significant improvement in outcomes for the majority of CRC patients. The one exception being immunotherapy for MSI hi CRCs, which account for approximately 15% of CRCs. For the remaining 85% of CRCs the standard of care chemotherapy regimens have not changed in decades. Targeted agents such as Bevacizumab and Avastin have been added but they typically extend life by months.  However, it is also important to acknowledge that approximately 60% of all CRC patients with metastatic disease initially respond to standard of care chemotherapy regimens, typically Irinotecan, 5-fluoruracil, and leucovorin (FOLFIRI). Indeed, a significant percentage of these patients demonstrate an impressive initial response to chemotherapy and some to the extent that CTs show no evidence of disease. However, the vast majority of these tumours will eventually stop responding and develop irreversible resistance. The dogma has been that these “chemoresponsive” cancer cells are dormant and therefore cannot be targeted. This biology is not unique to CRC, impressive initial responses to chemotherapy and/or targeted agents are seen in a wide range of malignancies. Cancer cells in this “chemoresponsive state” are now referred to as drug tolerant persisters (DTPs) and are emerging as key players in the field of non-genetic tumor heterogeneity across a wide range of tumors in response to therapy. DTPs are defined by a state of reversible resistance that cannot be explained on the basis of a genetic mutation.

The focus of my research program is to develop a better understanding of the drug tolerant persister state in colorectal cancer. More specifically, we want to understand the molecular pathways and survival strategies DTPs are harnessing to survive the stressful environment caused by chemotherapy and targeted agents. The overarching goal being to identify the “achilles heal” of DTPs and target them before they give rise to classical irreversible clonal resistance.