Grant: Doctoral Research Award: Canada Graduate Scholarships

Lin28, along with Sox2, Oct4, and Nanog, forms a critical network of genes known as the core stemness genes, which play a key role in transforming ordinary cells into pluripotent stem cells. In cancer, Lin28 is particularly important because it helps regulate these stemness genes, contributing to the growth and spread of tumors, especially those that resist treatment. Lin28's role in promoting cancer progression has made it a prime target for new drug development. Despite the potential of targeting Lin28, no effective small-molecule inhibitors have yet been approved for clinical use. Most existing research has used high-throughput screening methods, but the compounds identified so far have not been very effective or well-characterized. For instance, some compounds only work at very high concentrations and lack detailed information on how they interact with Lin28. Our approach involves using advanced computer-aided drug design (CADD) to find new drug candidates that specifically target Lin28. By analyzing the structure of Lin28 bound to its RNA targets, we aim to design compounds that can block this interaction. This method has already led us to discover a promising new compound, which effectively inhibits Lin28's ability to bind to RNA, suppresses cancer stem cell activities, and enhances the effects of chemotherapy drugs. This research highlights the potential of CADD in developing new cancer therapies. By focusing on disrupting Lin28's interactions with RNA, we aim to create more effective treatments to treat tumors that could lead to better patient outcomes and fewer drug resistance issues.