The androgen receptor (AR) is a key regulator of the growth and proliferation of prostate cancer. The majority of lethal castration-resistant prostate cancer (CRPC) growth is still dependent on AR activity. The AR need to be in the nucleus to exert its biological action as a transcription factor. As such, defining the mechanisms that regulate the subcellular localization of AR are important. Previously it was believed that AR was imported into the nucleus in a ligand-dependent manner and subsequently exported out of the nucleus upon ligand withdrawal. Recent evidence has challenged this decades-old paradigm and showed that the AR is degraded, not exported, in the nucleus. This review discusses the current understanding of how AR nucleocytoplasmic localization is regulated by import and through nuclear degradation.
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http://dx.doi.org/10.1016/j.mce.2023.112009 | DOI Listing |
Endocr Relat Cancer
January 2025
S Dehm, Masonic Cancer Center, University of Minnesota, Minneapolis, United States.
Treatment for castration-resistant prostate cancer (CRPC) primarily involves the suppression of androgen receptor (AR) activity using androgen receptor signaling inhibitors (ARSIs). While ARSIs have extended patient survival, resistance inevitably develops. Mechanisms of resistance include genomic aberrations at the AR locus that reactivate AR signaling, or lineage plasticity that drives emergence of AR-independent phenotypes.
View Article and Find Full Text PDFWorld J Urol
January 2025
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Propose: This study aimed to evaluate the efficacy and safety of neoadjuvant treatment of darolutamide, a next-generation androgen receptor inhibitor, plus androgen deprivation therapy (ADT) for patients with locally advanced prostate cancer (LAPC).
Methods: This single-arm, multicenter, open-label phase II trial (ClinicalTrials.gov: NCT05249712, 2022-01-01), recruited 30 localized high-risk/very high-risk prostate cancer (HRPCa/VHRPCa) patients from three centers in China between 2021 and 2023.
Alzheimers Dement
December 2024
University of California, San Diego, La Jolla, CA, USA.
Background: According to data from the Alzheimer's Association, more than two-thirds of patients living with Alzheimer's disease (AD) in the United States are women. The interplay between aging and hormone depletion during menopause has been proposed as a leading cause, but the molecular underpinnings of this vulnerability are not fully understood. On the one hand, approaches that seek to supplement estrogens to rescue pre-menopausal hormonal levels have had contradictory outcomes in clinical trials.
View Article and Find Full Text PDFEMBO Mol Med
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
Aggressive prostate cancer (PCa) variants associated with androgen receptor signaling inhibitor (ARSI) resistance and metastasis remain poorly understood. Here, we identify the axon guidance semaphorin receptor PlexinD1 as a crucial driver of cancer aggressiveness in metastatic castration-resistant prostate cancer (CRPC). High PlexinD1 expression in human PCa is correlated with adverse clinical outcomes.
View Article and Find Full Text PDFJ Endocrinol Invest
January 2025
Regional Reference Center for Gender Incongruence (CRRIG) of the Veneto Region, University Hospital of Padova, Padua, Italy.
Purpose: Previous studies show that transgender and gender-diverse (TGD) individuals, especially those assigned male at birth (AMAB), often have low bone mineral density (BMD) before beginning gender-affirming hormone therapy (GAHT). The reasons for this are not fully understood, and the potential role of androgen receptor (AR) polymorphisms - known to affect bone density in the general population - has not been explored. This study aims to assess the impact of AR polymorphisms on bone health in the TGD population.
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