Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications

• Main Authors: Gaetano Aurilio, Alessia Cimadamore, Roberta Mazzucchelli, Antonio Lopez-Beltran, Elena Verri, Marina Scarpelli, Francesco Massari, Liang Cheng, Matteo Santoni, Rodolfo Montironi
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: Cells
• Subjects: prostate cancer; androgen receptor; AR-V7; AR variants; AR antagonists; AR resistance
• Online Access: https://www.mdpi.com/2073-4409/9/12/2653

Around 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.