Project 463226

The long-term goal of our research program is to understand the molecular recognition process that takes place between a special type of protein involved in cancer development and drug molecules. Specifically, we seek to establish the best way to develop novel molecules with the ability to bind to, and inhibit, the cellular activity of oncoproteins. In this regard, we propose a relatively new approach that makes use of a common mechanism used by cells to identify, tag, and decompose proteins that are no longer useful. This mechanism uses special drug molecules that are capable of "turning on" the degradation of proteins involved in the development of cancer. This technology is known in the scientific literature as protein targeting chimeras or PROTACS, and it is the subject of multiple efforts by several pharmaceutical companies, some of them here in Canada, to bring new therapeutic agents to the clinic. This research grant will support the design and development of a series of novel molecules targeting the FOXM1 transcription factor in ovarian cancer cells, which is one of many proteins that are abnormally and consistently upregulated more than 75% of in high-grade serous carcinoma, which is the deadliest gynecologic malignancy accounting for most cases and deads in ovarian cancer. We expect that our work will provide evidence supporting the anti-tumour activity of FOXM1 PROTACs in ovarian cancer.