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Biological Chemistry

Microbiome Affects Cancer Drug Efficacy

Oncology: Mice with no gut bacteria don’t respond well to cancer therapies

by Sarah Everts
November 25, 2013 | APPEARED IN VOLUME 91, ISSUE 47

Gut bacteria help humans and other animals extract nutrients from food and fight pathogens. According to new research with mice, microorganisms colonizing digestive tracts also affect cancer drug efficacy.

Two groups report that the common cancer drugs cyclophosphamide, oxaliplatin, and cisplatin are not optimally effective in mice with tumors but no gut bacteria, or in those with gut bacteria knocked out by antibiotics (Science 2013, DOI: 10.1126/science.1240537; 10.1126/science.1240527).

“If what we discovered in mice is clinically relevant to humans,” then cancer patients and doctors should be aware that taking antibiotics could reduce the efficacy of chemotherapy, says Laurence Zitvogel of France’s National Institute of Health & Medical Research.

Antibiotic therapy is common for some cancer patients undergoing chemotherapy, specifically when the cancer drugs knock down the immune system leaving patients vulnerable to infection.

The two papers “provide unexpected but compelling evidence that intestinal microbiota play a strong role in the efficacy of cancer drug treatment outcomes,” comments Robert L. Hettich, a chemist at Oak Ridge National Laboratory who studies the human microbiome.

Both papers reveal that gut bacteria enable cancer therapies by helping to activate the mouse immune system, comments Eric G. Pamer, a medical researcher at Memorial Sloan-Kettering Cancer Center, in New York City. But the specific mechanisms are different, he adds.

The group led by Zitvogel found that during cyclophosphamide treatment, some gut bacteria can travel across the intestinal epithelium and get transported to mouse lymph nodes, where they help activate production of immune T cells that kill tumors.

Meanwhile, researchers have long known that cisplatin and oxaliplatin kill tumor cells by activating the production of reactive oxygen species. The second team, led by Giorgio Trinchieri and Romina S. Goldszmid of the NIH National Cancer Institute, found that in cisplatin- or oxaliplatin-treated mice, gut bacteria help prime immune cells to produce tumor-killing oxygen species.

The research will prompt oncologists to examine how their patients’ responses to chemotherapy correspond to their gut microbiomes, Pamer notes. They may also need to reconsider the use of antibiotics in patients receiving chemotherapy, he says.

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