Commonly used cancer drugs could be repurposed to help eliminate tapeworm infections, according to the first full genome analysis of the human gut pathogen.
A team led by Matthew Berriman, a geneticist who studies parasites at the Welcome Trust Sanger Institute in Hinxton, UK, sequenced the genomes of three human-infective tapeworm species as well as a fourth tapeworm that lives in the intestines of rats and mice. Their analysis, published online today of Nature found that among more than 1,000 gene products that are predicted to be druggable in the parasite responsible for echinococcosis—a disease that affects an estimated 2–3 million people worldwide—more than 200 already have existing therapies (many in the oncology space) that block them.
“By providing reference genomes for these tapeworms, the study lays the foundation for the identification of new potential drug targets to kill the worms,” says P’ng Loke, a microbiologist at the New York University Langone Medical Center who was not involved in the study.
The cancer link makes sense given the life cycle of the tapeworm, notes Berriman. People typically ingest the parasite as eggs or larvae that then migrate to the host’s intestines where they develop into adult tapeworms. “When larvae infiltrate tissues and organs and cause large proliferating growth, [it’s] like metastasizing cancer,” he says.
The potential for new pharmacological interventions doesn’t end there, though. The genome map also revealed that the tapeworm’s parasitic lifestyle has led to a number of gene losses and molecular simplifications that could provide a wormy Achilles’ heel. Thanks to evolution, for example, tapeworms have lost genes involved in oxidative stress response, making them reliant on just one enzyme for this kind of cell detoxification.
Fortunately, drug repurposing could prove successful here, too. The tapeworm enzyme involved in oxidative stress, called thioredoxin glutathione reductase, is the target of multiple drugs that have been shown to kill blood flukes and flatworms. “We have identified clear vulnerabilities in the pathways the parasites rely on,” Berriman says.