Stopping testosterone production can slow down tumor growth in the early stages of prostate cancer. On the other hand, increasing testosterone levels can help slow down the progression of the disease in patients with more advanced cancer. It has been challenging to understand how different amounts of the same hormone can have such different effects on prostate tumors which has made it difficult to create new treatments that take advantage of this knowledge.
A recent study evaluated how different amounts of androgens can change how androgen receptors (AR) behave, which can affect prostate cancer growth in different ways.
How Androgens Work
Low-Dose Androgens (LD): Low-dose androgens make certain cell signals that help cells grow, leading to more cancer cells. They also turn on genes that help control the cell cycle, which is how cells grow and divide.
High-Dose Androgens (HD): High-dose androgens help create pairs or groups of androgen receptors, which can actually slow down cancer growth instead. They help activate other important genes that are usually controlled by the androgen receptor.
Understanding the Mechanisms
- When the level of androgen changes, it affects how the androgen receptors work:
- AR Monomers (single receptors): These help the cells grow and divide more quickly, which can lead to increased tumor size.
- AR Dimers (paired receptors): These can prevent certain genes from being active, which helps limit cell growth.
- The way AR is grouped helps cells figure out how to react to the level of androgens in the body.
Implications for Treatment
- Some current treatments that aim to block the actions of AR may accidentally stop the good effects that the pairing of these receptors can have.
- Finding ways to increase the pairing of AR could be a new strategy to slow down cancer growth in prostate cancer cells.
This study shows that the amount of androgen can change the way androgen receptors affect prostate cancer growth. It highlights the importance of developing treatments that consider how these receptors work in different ways.
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Reference: Safi R, Wardell SE, Watkinson P, et al. Androgen receptor monomers and dimers regulate opposing biological processes in prostate cancer cells. Nat Commun. 2024 Sep 3;15(1):7675.
