Grant: Collaborative Health Research Projects (NSERC partnered)

"Cancer has or will affect the lives of virtually all Canadians. To develop drugs effective against a broad spectrum of cancers, we focus on a particularly potent gene-regulating protein called Myc, which contributes to approximately 50% of cancers and tumors. Developing inhibitors targeting Myc will mark a key advance, for experiments in mice show that even a moderate block to Myc activity can profoundly inhibit and even eradicate tumor growth. Although our idea is straightforward, targeting Myc has been difficult because the technologies were undeveloped. By combining the research strengths of three productive research labs (in chemistry, engineering, and cancer research), we can now move this idea forward to identify Myc inhibitors. Myc partners with protein Max to bind specific regions of DNA, called E-boxes, to regulate genes that can initiate cancer. We hypothesize that blocking the interaction of Myc/Max with the E-box DNA will kill cancer cells. Traditional drug screening approaches to identify drugs that interfere with this type of interaction have not been successful. Our innovative approach to solving this problem is to develop novel minimalist hybrid proteins (MHPs) that prevent Myc/Max and E-box DNA from binding to each other in the first place. We will accomplish this goal by mixing technologies from three different fields and using newly developed research tools to conduct the sophisticated development of specific Myc/Max:E-box inhibitors. Specifically, we will exploit a new platform of protein drug development that has recently been patented. This cutting-edge technology will be used to develop drugs that block Myc/Max interaction with E-box DNA. With our multi-pronged, highly interdisciplinary approach, we will identify potential MHP ""smart"" drugs that target one of the major causes of cancer, the Myc oncoprotein. Newly developed nanotechnology will provide the vehicles for delivery of MHPs to the cell nucleus. A new assay, called ChIP-chip, will be used to measure this activity in live cells. "