The MYC oncoprotein is a potent cancer driver. In normal cells, c-MYC (MYC) expression is highly regulated. However, in over 50% of human cancers, MYC is deregulated by a plethora of mechanisms leading to sustained and often elevated expression. As a master-regulator, MYC controls the transcription of ~10% of genes, thereby unleashing numerous biological processes essential for cancer growth and survival, resulting in aggressive disease. Our hypothesis is that inhibiting the oncogenic activity of MYC by blocking MYC protein-protein interactions that are essential for MYC to function as a cancer driver will provide a novel effective therapy for many human cancers.

To this end, we first identified the MYC proteome by conducting in-cell, proximity labeling followed by mass spectrometry (BioID). We focused on proteins that interacted with MYC through a region called MYC-Box 0 (MB0), which we have shown is essential for the full oncogenic activity of MYC and conserved amongst the MYC family of transforming oncoproteins (MYC, L-MYC, N-MYC). Indeed, we have shown that PNUTS, the regulatory subunit of the PP1 phosphatase interacts directly with MYC to control MYC phosphorylation and degradation. Development of MYC-PNUTS inhibitors are underway and will be discussed. In addition, several novel direct MYC(MB0) interactors that are required for MYC oncogenesis will be described. These new insights not only provide us with a better understanding of how MYC functions as a potent cancer driver but also provides new strategies to develop anti-MYC therapies to kill cancer cells.

Dr. Linda Penn is Senior Scientist at the Princess Margaret Cancer Centre and a Professor in the Medical Biophysics Department at the University of Toronto. She is also the Director of the University Health Network’s Office of Research Trainees. Dr. Linda Penn conducted her PhD at the University of Toronto and Hospital for Sick Children with Dr. Bryan Williams, focusing on interferon as an anti-viral. She then pursued her Post-Doctoral Fellowship at the Imperial Cancer Research Fund (ICRF) in London, UK with Drs. Hartmut Land and Gerard Evan to study the MYC oncogene in Cancer. Moving back to Canada, she established her research lab with a focus on i) the regulation and function of MYC in cancer, and ii) evaluating the role of statin drugs as anti-cancer agents.  She is a scientific advisor on several national/international review panels, serves on several journal editorial boards and is on the Board of the Terry Fox Research Institute. She has published >150 manuscripts and been honoured with several awards including the Canada Research Chair in Molecular Oncology (Tier 1), Woman-of-Action Award (Israel Cancer Research Fund), Award of Distinction (Leukemia Research Fund), Honorary Doctorate (University of Linkoping, Sweden), Richard Hill Mentorship Award and was recently appointed as a Senior Fellow of Massey College.