The Role of ERα and ERβ in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches

Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERβ functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERβ in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERβ in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.