University of Missouri
Early-Stage Drug Discovery Targeting a Marker of Pancreatic Cancer and its Metastasis
Aim: Basic Science / Cancer Biology
A bad omen of few months remaining to survive with pancreatic cancer is the protein-cutting enzyme called MMP-7. Pathologists showed that MMP-7 increases the size of the tumors and is very important for them to spread in the body. We found a chink in the armor of MMP-7 by determining its 3D atomic structure bound to a sugar chain. This chain is like those at cell surfaces that activate MMP-7. Atomwise, a company, did an exhaustive computer search for drug-like compounds that might prevent MMP-7 from interacting with the sugar chain on the cell surface. They sent us a diverse set of the most promising compounds. We will rank these compounds for ability to 1) stick to MMP-7, 2) block the activation of MMP-7 by the special sugar chains, and 3) impair the ability of epithelial tumor cells from pancreatic cancer to invade and spread in their surroundings. This will guide future work by identifying compounds ready to test in mice with pancreatic cancer and by either suggesting a starting point for drug optimization or revising our strategy to attack and monitor MMP-7 in pancreatic cancer.