Grant: Project Grant

Over 10,000 Canadians are diagnosed and ~3000 die from a type of blood cancer known as non-Hodgkin lymphoma each year, and improved therapies for this disease are urgently needed. cMYC is an essential regulator of gene expression in cancer cells. It is hyperactivated in >50% of all cancers, including many non-Hodgkin lymphomas. The hyperactivation of cMYC in the cancer cells is commonly linked to poor therapy response and inferior prognosis for the patients. Overall, cMYC is a highly important but challenging drug-target. In recent work we demonstrated a cooperation of cMYC with another protein and enzyme MYSM1 in the regulation of gene expression in cancer cells. We established that in mouse models with hyperactivated cMYC, the loss of MYSM1 activity is strongly protective against lymphoma, delaying disease progression and prolonging survival. This serves as a proof-of-concept for the targeting of MYSM1 in cancer cells as a novel therapy for cMYC-driven lymphoma. The current research program builds on this work and will: (1) analyze the cellular and molecular mechanisms through which the loss of MYSM1 activity protects against lymphoma, translating our studies from mouse to human preclinical cancer models, (2) conduct the first comprehensive structural analysis of MYSM1 protein and launch the development of chemical compounds to inhibit MYSM1 activity in cancer cells. The research program therefore represents an essential step toward translational development of MYSM1 as a drug-target for non-Hodgkin lymphoma and other blood cancers with hyperactivated cMYC.