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Metabolomic effects of androgen deprivation therapy treatment for prostate cancer.

Publication ,  Journal Article
Chi, J-T; Lin, P-H; Tolstikov, V; Oyekunle, T; Chen, EY; Bussberg, V; Greenwood, B; Sarangarajan, R; Narain, NR; Kiebish, MA; Freedland, SJ
Published in: Cancer Med
June 2020

Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6 months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT-associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3-hydroxybutyric acid and ketogenesis. Third, many acyl-carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3-formyl indole (a.k.a. indole-3-carboxaldehyde), a microbiota-derived metabolite from the dietary tryptophan. Indole-3-carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT-associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT-linked comorbidities and diabetes risk.

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Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

June 2020

Volume

9

Issue

11

Start / End Page

3691 / 3702

Location

United States

Related Subject Headings

  • Prostatic Neoplasms
  • Prospective Studies
  • Prognosis
  • Metabolome
  • Male
  • Lipids
  • Lipidomics
  • Humans
  • Follow-Up Studies
  • Case-Control Studies
 

Citation

APA
Chicago
ICMJE
MLA
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Chi, J.-T., Lin, P.-H., Tolstikov, V., Oyekunle, T., Chen, E. Y., Bussberg, V., … Freedland, S. J. (2020). Metabolomic effects of androgen deprivation therapy treatment for prostate cancer. Cancer Med, 9(11), 3691–3702. https://doi.org/10.1002/cam4.3016
Chi, Jen-Tsan, Pao-Hwa Lin, Vladimir Tolstikov, Taofik Oyekunle, Emily Y. Chen, Valerie Bussberg, Bennett Greenwood, et al. “Metabolomic effects of androgen deprivation therapy treatment for prostate cancer.Cancer Med 9, no. 11 (June 2020): 3691–3702. https://doi.org/10.1002/cam4.3016.
Chi J-T, Lin P-H, Tolstikov V, Oyekunle T, Chen EY, Bussberg V, et al. Metabolomic effects of androgen deprivation therapy treatment for prostate cancer. Cancer Med. 2020 Jun;9(11):3691–702.
Chi, Jen-Tsan, et al. “Metabolomic effects of androgen deprivation therapy treatment for prostate cancer.Cancer Med, vol. 9, no. 11, June 2020, pp. 3691–702. Pubmed, doi:10.1002/cam4.3016.
Chi J-T, Lin P-H, Tolstikov V, Oyekunle T, Chen EY, Bussberg V, Greenwood B, Sarangarajan R, Narain NR, Kiebish MA, Freedland SJ. Metabolomic effects of androgen deprivation therapy treatment for prostate cancer. Cancer Med. 2020 Jun;9(11):3691–3702.
Journal cover image

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

June 2020

Volume

9

Issue

11

Start / End Page

3691 / 3702

Location

United States

Related Subject Headings

  • Prostatic Neoplasms
  • Prospective Studies
  • Prognosis
  • Metabolome
  • Male
  • Lipids
  • Lipidomics
  • Humans
  • Follow-Up Studies
  • Case-Control Studies