Aurilio, GaetanoCimadamore, AlessiaMazzucchelli, RobertaLopez-Beltran, AntonioVerri, ElenaScarpelli, MarinaMassari, FrancescoCheng, LiangSantoni, MatteoMontironi, Rodolfo2022-04-202022-04-202020-12Aurilio G, Cimadamore A, Mazzucchelli R, Lopez-Beltran A, Verri E, Scarpelli M, Massari F, Cheng L, Santoni M, Montironi R. Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications. Cells. 2020 Dec 10;9(12):2653. doi: 10.3390/cells9122653. PMID: 33321757; PMCID: PMC7763510.https://hdl.handle.net/1805/28596Around 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.en-USAttribution 4.0 United StatesProstate cancerAndrogen receptorAR variantsAR antagonistsAR resistanceArticle