Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy
Authors:Safae Terrisse1, Laurence Zitvogel2-5 and Guido Kroemer6-8
doi: 10.15698/mic2022.12.787
Volume 9, pp. 190 to 194, published 15/11/2022.
1 Medical Oncology, Hôpital Saint-Louis, Paris, France.
2 INSERM U1015, Equipe Labellisée – Ligue Nationale contre le Cancer, Villejuif, France.
3 University Paris Saclay, Gif-sur-Yvette, France.
4 Gustave Roussy, ClinicObiome, Villejuif, France.
5 Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
6 Equipe labellisée par la Ligue contre le Cancer, Université de Paris Cité, Sorbonne Université, Institut Universitaire de France, Inserm U1138, Centre de Recherche des Cordeliers, Paris, France.
7 Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.
8 Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
Keywords:
Akkermansia muciniphila, castration-resistant prostate cancer, hormonotherapy, microbiome, Ruminococcus gnavus
Corresponding Author(s):
Conflict of interest statement:
GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys, and Vascage. GK has been consulting for Reithera. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Thera-peutics and Therafast Bio. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. GK’s brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. LZ has held research contracts with 9 Meters Biopharma, Daiichi Sankyo, Pilege, was on the on the Board of Directors of Transgene, is a cofound-er of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota.
Please cite this article as:
Safae Terrisse, Laurence Zitvogel and Guido Kroemer (2022). Effects of the intestinal microbi-ota on prostate cancer treatment by androgen deprivation therapy. Microbial Cell 9(12): 190-194. doi: 10.15698/mic2022.12.787
© 2022 Terrisse et al.. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.
Abstract:
Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.