A group of scientists has identified the role of progesterone in advanced prostate cancer and found a potential therapeutic target to suppress the generation of progesterone.
According to the Global Cancer Observatory, in 2020, there were more than 100,000 new cases of prostate cancer in China. Based on previous studies, the development of prostate cancer is sustained by androgens. As treatment options, androgen deprivation therapy (ADT) significantly reduces the amount of circulating testosterone to castration levels, while abiraterone works to decrease the amount of androgen in the body. When used in combination, it leads to an androgen-deficient environment in patients. However, disease progression is inevitable.
In a study published in Cell Reports Medicine, a group of researchers led by Li Zhenfei of the CAS Center for Excellence in Molecular Cell Science of the Chinese Academy of Sciences revealed the oncometabolite role of progesterone in advanced prostate cancer and proposed strategies to eliminate its oncogenic effect as an aspect of prostate cancer treatment.
Here, the team investigated alteration in the metabolomics of abiraterone-resistant patients and observed that one metabolite, progesterone, increased significantly. They found that transient treatment with high doses of progesterone would trigger multiple pathways to encourage the proliferation of cancer cells, while long-term treatment with progesterone at a low dosage will increase the expression of GATA2, resulting in an irreversible alteration in the transcriptome that produces disease progression.
The team also looked into the metabolic pathway of progesterone and identified the enzyme 3βHSD1 as a potential therapeutic target for preventing the generation of progesterone. Specifically, they discovered that biochanin-A, an isoflavone rich in soy and other foods, is a 3βHSD1 inhibitor and restricts prostate cancer development.
Based on the cancer-causing effects of progesterone, plasma progesterone levels were observed to be negatively correlated with the duration of abiraterone treatment. This means that progesterone might be a potential predictive biomarker for abiraterone response and as of now, related clinical research is still underway.
From this study, the team has demonstrated that biochanin-A inhibits 3βHSD1, thereby restricting the cancer-causing effects of progesterone and curbing the development of prostate cancer.
Source: Hou et al. (2022). Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer. Cell Reports Medicine, 3(3), 100561.