See also recent threads.
New paper below [1] & [2].
[1] Editorial:
"Prostate cancer is driven by androgens (particularly testosterone), so androgen deprivation therapy (ADT) is the standard of care for patients with advanced prostate cancer. After an initial response, hormone-sensitive prostate cancer (HSPC) usually progresses to castration-resistant prostate cancer (CRPC) owing to various mechanisms that may include altered androgen receptor (AR) signaling and intratumor accumulation of androgens even during ADT. On page 216 of this issue, Pernigoni et al. (1) show that gut commensal bacteria that are able to synthesize the sex hormone precursor dehydroepiandrosterone (DHEA) and testosterone increase in patients and mice with CRPC and prevent complete suppression of androgens during ADT. In mice, these androgen-producing bacteria can be targeted to slow progression from HSPC to CRPC."
[2] 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
Abstract
"The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. 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. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens."
-Patrick
[1] pubmed.ncbi.nlm.nih.gov/346...
Science
. 2021 Oct 8;374(6564):154-155. doi: 10.1126/science.abl7070. Epub 2021 Oct 7.
Gut bacteria enable prostate cancer growth
John A McCulloch 1 2 , Giorgio Trinchieri 3
Affiliations collapse
Affiliations
1 Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
2 Genetics and Microbiome Core, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
3 Cancer Immunobiology Section, Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
PMID: 34618567 DOI: 10.1126/science.abl7070
science.org/doi/10.1126/sci...
Gut bacteria enable prostate cancer growth
JOHN A. MCCULLOCH AND GIORGIO TRINCHIERI
SCIENCE
•
8 Oct 2021
•
Vol 374, Issue 6564
•
pp. 154-155
•
DOI: 10.1126/science.abl7070
GET ACCESS
Abstract
References and Notes
0eLetters
Abstract
Prostate cancer is driven by androgens (particularly testosterone), so androgen deprivation therapy (ADT) is the standard of care for patients with advanced prostate cancer. After an initial response, hormone-sensitive prostate cancer (HSPC) usually progresses to castration-resistant prostate cancer (CRPC) owing to various mechanisms that may include altered androgen receptor (AR) signaling and intratumor accumulation of androgens even during ADT. On page 216 of this issue, Pernigoni et al. (1) show that gut commensal bacteria that are able to synthesize the sex hormone precursor dehydroepiandrosterone (DHEA) and testosterone increase in patients and mice with CRPC and prevent complete suppression of androgens during ADT. In mice, these androgen-producing bacteria can be targeted to slow progression from HSPC to CRPC.
***
[2] science.org/doi/10.1126/sci...
Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis
NICOLÒ PERNIGONI HTTPS://ORCID.ORG/0000-0001-5115-8447ELENA ZAGATO HTTPS://ORCID.ORG/0000-0001-6756-3674ARIANNA CALCINOTTO HTTPS://ORCID.ORG/0000-0003-1746-6424MARTINA TROIANIRICARDO PEREIRA MESTRE HTTPS://ORCID.ORG/0000-0002-3123-3697BIANCA CALÌ HTTPS://ORCID.ORG/0000-0002-9090-9992GIUSEPPE ATTANASIOJACOPO TROISI HTTPS://ORCID.ORG/0000-0003-2962-7379MIRKO MININI HTTPS://ORCID.ORG/0000-0001-9780-4643[...]ANDREA ALIMONTI HTTPS://ORCID.ORG/0000-0002-9362-2313 +32 authors Authors Info & Affiliations
SCIENCE
•
8 Oct 2021
•
Vol 374, Issue 6564
•
pp. 216-224
•
DOI: 10.1126/science.abf8403
GET ACCESS
Microbes hijack prostate cancer therapy
Abstract
Supplementary Materials
References and Notes
0eLetters
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
Abstract
The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. 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. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.
