Project 459075

Lymphoma is the 6th most common form of cancer in Canada, with one in 38 Canadians expected to develop lymphoma during their lifetime. While advances in treatment options over the past two decades have drastically improved survival rates in some forms of lymphoma, many of the more aggressive forms of lymphoma remain an unmet clinical need due to poor outcomes. High grade B-cell lymphoma (HGBL) is an aggressive form of lymphoma associated with low survival rates. Efforts to cure HGBL have been limited to using more intense combinations of chemotherapy. This strategy has been unsuccessful, curing less than half of patients. Additionally, a consequence of this strategy is that intensified chemotherapy leads to increased toxicity, resulting in frequent hospitalizations, which comes at a significant burden to patients and a high financial toll on the healthcare system. Improving the treatment of HGBL is limited by our poor understanding of this disease. HGBL is distinguished from other types of lymphoma using methods established decades ago which fail to capture the true complexity of the disease. Advances in technology have allowed us to recognize that cancer subtypes can be further refined by grouping patients based on the genetic features of their tumours, with patients in these refined subgroups sharing similar responses to treatment. This has led to the establishment of "precision medicine", where patients are grouped by key genetic features of their cancer and receive treatments targeting these specific features. Through revealing the genetic basis of HGBL, this project aims to identify before treatment the patients in whom chemotherapy will be ineffective. Further, we aim to develop new treatment strategies by identifying therapeutic targets that are specific to these patients. With the demonstrated ineffectiveness of intensified chemotherapy, precision medicine is the best way forward in improving the dismal outcomes of patients with HGBL.