A research collaboration between British and Swiss scientists has shown in a preclinical study how bacteria in the gut can contribute to both the progression of advanced prostate cancer and developing resistance to hormone therapy.
The findings are published in the journal Science in a paper titled, “Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.”
“The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts,” the researchers wrote. “The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice.”
A team of scientists from the Institute of Cancer Research, London; the Institute of Oncology Research in Bellinzona, Switzerland; and the Swiss Federal Institute of Technology used mice and patient samples to investigate the role of gut bacteria in prostate cancer growth and progression.
Scientists found that getting rid of all gut bacteria in mice with prostate cancer slowed tumor growth and delayed the emergence of hormone resistance. They also discovered that transplanting feces from mice with hormone-resistant prostate cancer into mice with low androgen levels that had not yet developed resistance encouraged tumor growth.
The researchers further analyzed the gut bacteria from patients who were being treated at the Royal Marsden NHS Foundation Trust.
“Our findings reveal that the initiation of hormone therapy for prostate cancer can trigger ‘gut bugs’ to start producing androgen hormones,” explained Johann de Bono, M.D., Ph.D., study author and professor of experimental cancer medicine at the Institute of Cancer Research, London, and consultant medical oncologist at the Royal Marsden NHS Foundation Trust. “These androgens can then sustain prostate cancer’s growth and drive resistance to hormone therapy—worsening men’s survival outcomes.”
“The influence of the gut microbiome on cancer is a fascinating new area of science that we are just beginning to understand,” added Kristian Helin, Ph.D., chief executive of the Institute of Cancer Research, London. “These exciting findings are the first to unveil a mechanism through which the gut microbiome can drive prostate cancer growth and resistance to hormone therapy.
“Understanding how common, ‘good’ bacteria in the gut—which play a vital role in keeping us healthy—can interfere with hormone metabolism in men with prostate cancer could help us devise new treatment strategies. I look forward to this research moving forward into the clinic and hope that strategies to manipulate the microbiome could make a real difference for patients.”
The findings pave the way for potentially treating advanced or hormone-resistant prostate cancer through manipulation of the microbiome.
“Our discoveries pave the way to adjuvant therapeutic strategies that, through microbiota manipulations, counteract the expansion of androgen-producing bacterial species,” concluded Andrea Alimonti, head of molecular oncology at the Institute of Oncology Research (IOR), and professor at Università della Svizzera italiana (USI), at the University of Padova, and at the Swiss Federal Institute of Technology (ETH).