Robert Korneluk, PhD, FRSC
Senior Scientist, CHEO Research Institute
Distinguished Professor, Departments of Biochemistry, Microbiology and Immunology, and Pediatrics, Faculty of Medicine, University of Ottawa
Director, Apoptosis Research Centre (ARC), CHEO Research Institute
Head, Solange Gauthier Karsh Molecular Genetics Laboratory (CHEO Research Institute)
Scientific Co-founder of Aegera Therapeutics Inc. (Montreal)
Howard Hughes Medical Institute International Research Scholar, for three terms (1997-2001)

Abstract: The Inhibitors of Apoptosis (IAPs) are multifunctional proteins with roles in cell death, signalling, innate immunity and oncogenesis. Two IAP family members (cIAP1 and cIAP2) control, through their E3 ubiquitin ligase functions, the assembly and activity of key regulatory complexes in the NF-kB signalling
pathway. Small molecule compounds that target the IAPs, known as Smac mimetics, are currently under intense clinical development for the treatment of cancer. Smac mimetics preferentially sensitize tumor cells, compared to normal cells, to the death-inducing properties of cytokines, in particular TNF and TRAIL. To date, no effective approach at providing these cytokine death triggers to a cancer patient, in combination with a Smac mimetic, has been attempted. We have shown in preclinical mouse models of cancer that the administration of oncolytic viruses, or synthetic Toll-receptor agonists, can induce a systemic but safe cytokine storm, which potently synergizes with Smac mimetics to effectively eradicate tumors. We predict that this simple combinatorial cancer immunotherapy approach, which can be easily tested in the clinic, will ultimately become a standard of care for the treatment of cancer.

Apoptosis - Cancer- Tumor cells