The Role of the Androgen Receptor in Prostate Cancer

Prostate cancer often depends on the androgen receptor (AR), a protein that promotes cancer cell growth. A common and dangerous stage of the disease is castration- resistant prostate cancer (CRPC), which continues to grow even after treatments that lower male hormones. One major reason this happens is that cancer cells make too much AR. CRPC cells can increase AR levels in several ways. One way is to copy the AR gene, thereby increasing the amount of AR produced. However, many tumors have high AR levels without extra gene copies, suggesting that other controls are also important.

Special DNA regions, such as enhancers and promoters, play a key role in switching on the AR gene. These regions can loop over and interact with the AR gene to boost its activity . Some enhancers are located far upstream, within, or downstream of the gene. In CRPC, these enhancers often become more active or are copied more frequently , thereby increasing AR production.

Several different proteins help control these enhancers; one increases AR production by activating a promoter near the gene. Another is inside the gene and increases AR levels in advanced cancer. Other enhancers may also help drive AR overproduction, especially after a drug.

AR overexpression in CRPC is driven by multiple DNA regions and proteins, not just the AR gene. Learning how these enhancers work could lead to treatments that better block AR and slow advanced prostate cancer.

Nature, Jan. 2026.