A study from Karolinska Institutet in Sweden shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA. [Darryl Leja
Credit: Darryl Leja

Androgen deprivation therapy for prostate cancer involves depriving the cancer cells of this fuel by either blocking the production or action of androgen hormones. Although hormone therapy plays an important role in treating patients with advancing prostate cancer, it is increasingly being used to treat localized disease as well. However, hormone therapy alone does not cure prostate cancer, it is usually used in combination with other treatments.

Researchers at CAS Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences demonstrate in mice the oncometabolite role of progesterone in advanced prostate cancer and strategies to eliminate its oncogenic effect.

Their findings are published in the journal Cell Reports Medicine.

“Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens,” wrote the researchers. “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.”

The researchers investigated alteration in the metabolomics of abiraterone-resistant patients and found that one metabolite—progesterone—increased significantly. Transient treatment with high doses of progesterone will activate multiple pathways to promote the proliferation of cancer cells. Long-term treatment with progesterone at a low dosage will increase the expression of GATA2, resulting in an irreversible alteration in the transcriptome that promotes disease progression.

They also investigated the metabolic pathway of progesterone. They identified the enzyme 3bHSD1 as a potential therapeutic target for eliminating the generation of progesterone.

Their findings suggest progesterone might be a potential predictive biomarker for abiraterone response and related clinical research is in progress.

“In summary, this work identified progesterone as an oncogenic hormone in prostate cancer patients receiving abiraterone treatment,” concluded the researchers. “BCA was discovered as a potent 3βHSD1 inhibitor and prevented the oncogenic effects of progesterone by suppressing the synthesis of progesterone. Higher plasma levels of progesterone are correlated with poor clinical outcomes of abiraterone treatment in patients.”

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