Cancer Drug Interactions Revealed

The detailed manner by which the cancer drug etoposide interacts with its enzyme target, topoisomerase II, has been revealed for the first time. Etoposide, the most widely prescribed anticancer drug in the world until the development of paclitaxel, is in its third decade of approved clinical use to treat a variety of cancers, including leukemias, lymphomas, and solid tumors. But the interactions of the drug with topoisomerase II had never been identified, until now. Neil Osheroff of Vanderbilt University School of Medicine; David E. Graves of the University of Alabama, Birmingham; and coworkers used saturation transfer difference NMR spectroscopy to identify the points of contact and their functional significance (Biochemistry, DOI: 10.1021/bi700272u). They find that three of etoposide's five rings interact with the enzyme, while the other two rings and the drug's glycosidic moiety do not. The study has "predictive value that may contribute to the future development of etoposide derivatives with greater activity against topoisomerase II," the researchers write.