Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis

Nicolò Pernigoni(Institute of Oncology Research), Elena Zagato(Institute of Oncology Research), Arianna Calcinotto(Institute of Oncology Research), Martina Troiani(Institute of Oncology Research), Ricardo Pereira Mestre(Ente Ospedaliero Cantonale), Bianca Calì(Institute of Oncology Research), Giuseppe Attanasio(Institute of Oncology Research), Jacopo Troisi(University of Salerno), Mirko Minini(Institute of Oncology Research), Simone Mosole(Institute of Oncology Research), Ajinkya Revandkar(Institute of Oncology Research), Emiliano Pasquini(Institute of Oncology Research), Angela Rita Elia(Institute of Oncology Research), Daniela Bossi(Institute of Oncology Research), Andrea Rinaldi(Institute of Oncology Research), Pasquale Rescigno(Candiolo Cancer Institute), Penny Flohr(Royal Marsden NHS Foundation Trust), Joanne Hunt(Royal Marsden NHS Foundation Trust), Antje Neeb(Royal Marsden NHS Foundation Trust), Lorenzo Buroni(Royal Marsden NHS Foundation Trust), Christina Guo(Royal Marsden NHS Foundation Trust), Jonathan Welti(Royal Marsden NHS Foundation Trust), Matteo Ferrari(Ente Ospedaliero Cantonale), Matteo Grioni(IRCCS Ospedale San Raffaele), Josée Gauthier(University of Florida), Raad Z. Gharaibeh(University of Florida), Anna Palmisano(Vita-Salute San Raffaele University), Gladys Martinetti Lucchini(Ente Ospedaliero Cantonale), Eugenia D’Antonio(Ente Ospedaliero Cantonale), Sara Merler(University of Verona), Marco Bolis(Mario Negri Institute for Pharmacological Research), Fabio Grassi(Università della Svizzera italiana), Antonio Esposito(Vita-Salute San Raffaele University), Matteo Bellone(IRCCS Ospedale San Raffaele), Alberto Briganti(Vita-Salute San Raffaele University), María Rescigno(Humanitas University), Jean‐Philippe Theurillat(Institute of Oncology Research), Christian Jobin(University of Florida), Silke Gillessen(Ente Ospedaliero Cantonale), Johann S. de Bono(Royal Marsden NHS Foundation Trust), Andrea Alimonti(Board of the Swiss Federal Institutes of Technology)
Science
October 8, 2021
Cited by 318

Abstract

Microbes hijack prostate cancer therapy Androgens such as testosterone and dihydrotestosterone are essential for male reproduction and sexual function. Androgens can also influence the growth of prostate tumor cells, and androgen deprivation therapy (ADT) either by surgical means (castration) or pharmacological approaches (hormone suppression), is the cornerstone of current prostate cancer treatments. Pernigoni et al . found that when the body was deprived of androgens during ADT, the gut microbiome could produce androgens from androgen precursors (see the Perspective by McCulloch and Trinchieri). Gut commensal microbiota in ADT-treated patients or castrated mice produced androgens that were absorbed into the systemic circulation. These microbe-derived androgens appeared to favor the growth of prostate cancer and helped to facilitate development into a castration- or endocrine therapy–resistant state. —PNK


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