Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis

Author:

Pernigoni Nicolò12ORCID,Zagato Elena12ORCID,Calcinotto Arianna12ORCID,Troiani Martina12,Mestre Ricardo Pereira3ORCID,Calì Bianca12ORCID,Attanasio Giuseppe12,Troisi Jacopo4ORCID,Minini Mirko12ORCID,Mosole Simone12,Revandkar Ajinkya12,Pasquini Emiliano12,Elia Angela Rita12,Bossi Daniela12,Rinaldi Andrea12ORCID,Rescigno Pasquale5ORCID,Flohr Penny6,Hunt Joanne6,Neeb Antje6,Buroni Lorenzo6,Guo Christina6ORCID,Welti Jonathan6,Ferrari Matteo3,Grioni Matteo7ORCID,Gauthier Josée8ORCID,Gharaibeh Raad Z.8ORCID,Palmisano Anna910ORCID,Lucchini Gladys Martinetti11,D’Antonio Eugenia3ORCID,Merler Sara1213ORCID,Bolis Marco1214ORCID,Grassi Fabio15,Esposito Antonio910ORCID,Bellone Matteo7ORCID,Briganti Alberto1617,Rescigno Maria1819ORCID,Theurillat Jean-Philippe12,Jobin Christian82021ORCID,Gillessen Silke23ORCID,de Bono Johann6ORCID,Alimonti Andrea121222ORCID

Affiliation:

1. Institute of Oncology Research, Oncology Institute of Southern Switzerland, CH-6500 Bellinzona, Switzerland.

2. Faculty of Biomedical Sciences, Università della Svizzera Italiana, CH-1011 Lugano, Switzerland.

3. Medical Oncology Unit, Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, 6500 Bellinzona, Switzerland.

4. Theoreo Srl, Montecorvino Pugliano, 84090 Salerno, Italy.

5. Candiolo Cancer Institute, FPO-IRCCS, Candiolo, 10060 Turin, Italy.

6. Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK.

7. Cellular Immunology Unit, IRCCS Ospedale San Raffaele, 20100 Milan, Italy.

8. Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Florida College of Medicine, Gainesville, FL, USA.

9. Experimental Imaging Center, San Raffaele Scientific Institute, 20100 Milan, Italy.

10. School of Medicine, University Vita–Salute San Raffaele, Milan, Italy.

11. Clinical Microbiology Unit, Ente Ospedaliero Cantonale, EOC, CH-6500 Bellinzona, Switzerland.

12. Department of Medicine, Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy.

13. Section of Oncology, Department of Medicine, University of Verona, 37134 Verona, Italy.

14. Computational Oncology Unit, Department of Oncology, Istituto di Ricerche Farmacologiche “Mario Negri” IRCCS, 20156 Milano, Italy.

15. Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.

16. Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.

17. University Vita–Salute San Raffaele, Milan, Italy.

18. IRCCS Humanitas Research Hospital, 20089 Rozzano, Milan, Italy.

19. Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy.

20. Department of Infectious Diseases and Immunology, University of Florida College of Medicine, Gainesville, FL, USA.

21. Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL, USA.

22. Department of Health Sciences and Technology, Eidgenössische Technische Hochschule (ETH) Zürich, Zurich, Switzerland.

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

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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