Gut microbes in patients who have undergone androgen deprivation therapy (ADT) for advanced prostate cancer, and microbes in similar mouse models, can produce androgens that circulate in the body. This discovery by Nicolò Pernigoni and colleagues could help explain why some patients develop ADT resistance, and may lead to the development of treatments that focus on the gut microbiome to overcome this resistance. Androgens promote the growth of prostate tumor cells, and ADT is the most common treatment for patients with advanced prostate cancer. Patients often develop ADT resistance, however, leading to tumor growth with an unfavorable prognosis. Pernigoni et al. found androgen deprivation in prostate cancer patients and mouse models promoted the expansion of specific gut bacteria that could synthesize androgens, leading to sustained tumor growth in the mice. Using antibiotics to kill off the gut bacteria in mice delayed ADT resistance. Fecal transplants from patients and mice who remained sensitive to ADT could control tumor growth in resistant mice, the researchers also found. John McCulloch and Giorgio Trinchieri discuss these results in a related Perspective.
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