Some metabolized cancer drugs are reactivated by bacteria in the gut as they pass through, causing severe diarrhoea. Matthew Redinbo at the University of North Carolina at Chapel Hill and his colleagues have identified the molecular structure of a key bacterial enzyme responsible, and have found several chemicals that prevent the reactivation.
The small-molecule inhibitors block the active site of the enzyme, called β-glucuronidase, without killing the resident bacteria or harming mammalian cells, which produce a slightly different version of the enzyme. One inhibitor protected mice from diarrhoea and colon damage caused by the drug irinotecan. Similar treatment could allow cancer patients to tolerate higher, more effective doses of chemotherapy, the researchers say.