2020
DOI: 10.3390/cells9122653
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Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications

Abstract: 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 res… Show more

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Cited by 146 publications
(100 citation statements)
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“…In the nucleus, the AR binds to ARE located on the DNA promoter via zinc finger binding domains. Once the AR dimer is bound to the DNA, it forms complexes with transcriptional coactivators and co-regulators for the regulation of target gene expression (Figure 1) [4,6,[14][15][16][17][18]. Coregulators are not DNA-binding proteins, but are recruited to transcription factors, such as the AR, and have different activities involved in the regulation of gene expression; some of them cause chromatin reconfiguration or are needed to bind some other cofactors [19].…”
Section: Activation Of Androgen Receptor and Cofactorsmentioning
confidence: 99%
See 1 more Smart Citation
“…In the nucleus, the AR binds to ARE located on the DNA promoter via zinc finger binding domains. Once the AR dimer is bound to the DNA, it forms complexes with transcriptional coactivators and co-regulators for the regulation of target gene expression (Figure 1) [4,6,[14][15][16][17][18]. Coregulators are not DNA-binding proteins, but are recruited to transcription factors, such as the AR, and have different activities involved in the regulation of gene expression; some of them cause chromatin reconfiguration or are needed to bind some other cofactors [19].…”
Section: Activation Of Androgen Receptor and Cofactorsmentioning
confidence: 99%
“…The genomic pathway of the AR starts with the binding of DHT to the receptor in the cytoplasm; AR is released from heat shock protein and translocated into the nucleus, dimerizes, and then binds to the androgen response element [15]. However, many of the cellular responses do not require transcription mediated by the AR, because AR binding to DHT is able to associate with molecular substrates in the cytoplasm and membrane to activate intracellular kinase cascades; and these actions are known as the non-genomic signaling of the AR.…”
Section: Ar Signaling and Bladder Cancer Progressionmentioning
confidence: 99%
“…Prostate cancer (PCa) is the most commonly occurring cancer in men and remains a leading cause of death in western countries [ 1 ]. The growth of prostate cancer cells depends on the androgen axis and the transcriptional activation of the androgen receptor (AR) by its natural ligands testosterone (T) or dihydrotestosterone (DHT) [ 2 ]. This led to the approval of androgen deprivation therapy (ADT) with GnRH agonists or antagonists as the standard of care in first line treatment of locally advanced or metastatic disease.…”
Section: Introductionmentioning
confidence: 99%
“…In presence of a germline BRCA alteration, ctDNA analysis was able to detect it in 100% of the cases. It is worth noticing that in the near future, other genetic alterations such as mutations in AR or in PIK3CA/AKT1/PTEN should be included in molecular analysis since target therapy is currently under investigation ( Table 2 ) [ 34 , 35 , 43 , 44 , 45 , 46 ].…”
Section: Circulating Tumor Dna In Prostate Cancermentioning
confidence: 99%