Inhibiting 31βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer

Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens. In this study, mass-spectrometry-based screening of clinical specimens and a retrospective analysis on the clinical data of prostate cancer patients indicate the potential oncogenic effects of progesterone in patients. High doses of progesterone activate canonical and non-canonical androgen receptor (AR) target genes. Physiological levels of progesterone facilitate cell proliferation via GATA2. Inhibitors of 3(3-hydroxysteroid dehydrogenase 1 (3(3 beta HSD1) has been discovered and shown to suppress the generation of progesterone, eliminating its transient and accumulating oncogenic effects. An increase in progesterone is associated with poor clinical outcomes in patients and may be used as a predictive biomarker. Overall, we demonstrate that progesterone acts as an oncogenic hormone in prostate cancer, and strategies to eliminate its oncogenic effects may benefit prostate cancer patients.

Automated summary

In this study, it was found that progesterone has oncogenic effects in prostate cancer patients, activating androgen receptor target genes and promoting cell proliferation. Inhibiting the generation of progesterone may eliminate its oncogenic effects, and increased levels of progesterone could serve as a predictive biomarker for poor clinical outcomes.