Grant: Project Grant

Cancer cells differ from normal cells in many ways that allow them to grow out of control and become invasive. That is why one major goal of anticancer therapy is to suppress cancer cell growth. DNA topoisomerase II (TOP2) genes, TOP2A and TOP2B, are two key genes to control cancer cell growth/division. TOP2A is essential for a parent cell to divide into two daughter cells, while TOP2B is important for cancer cells to increase oncogenes that promote cell division. Blocking both TOP2A and TOP2B would create a double-bolt lock to inhibit cancer cell growth. Although several TOP2 blockers are used as drugs to treat cancer patients, they are also toxic to normal cells and in some cases can transform normal cells into tumors. These limitations urge researchers to discover new inhibitors that block TOP2 activity through different mechanisms so that there will be less toxic effects on normal cells. In this study, we will build complex software incorporated with computer clusters to screen millions of chemicals from a chemical bank and then test these chemicals for their inhibitory effects on TOP2 activity. We will decipher how these chemicals inhibit TOP2 activity at the molecular level and determine whether these chemicals block cancer cell growth. This study will lead to the discovery of new TOP2 inhibitors as potential anticancer drugs.