Here we report the characteristics of a novel AR mutation A748T located in helix 5 of the ligand-binding domain, which was identified in metastatic prostate cancer.
While modern therapies for metastatic prostate cancer (PCa) have improved survival they are associated with an increasingly prevalent entity, aggressive variant PCa (AVPCa), lacking androgen receptor (AR) expression, enriched for cancer stem cells (CSCs), and evidencing epithelial-mesenchymal plasticity with a varying extent of neuroendocrine transdifferentiation.
We apply our method to non-recurrent primary and metastatic prostate cancer data, and identify the androgen receptor gene (AR) among the top genetic mediators and the AR pathway as a highly enriched pathway for metastatic prostate cancer.
In a specimen derived from metastatic prostate cancer we have reported a point mutation in the AR gene that leads to a single amino acid exchange in the ligand binding domain of the receptor.
This same AR mutation has been reported previously in a metastatic prostate cancer cell line, LNCaP, where this mutation confers upon the AR an altered ligand-binding specificity which is stimulated by estrogens, progestagens, and antiandrogens.
Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey-Holden Prostate Cancer Academy Meeting.
A consistent finding is that androgen receptor (AR) gene mutations, present in metastatic prostate cancer and in human prostate cancer cell lines as well as in xenograft and other animal models, result in decreased specificity of ligand-binding and inappropriate receptor activation by estrogens, progestins, adrenal androgens, glucocorticoids and/or AR antagonists.
Updates to the NCCN Guidelines for Prostate Cancer include further refinements in taking a family history, new recommendations for germline and somatic testing, use of androgen receptor blockers for nonmetastatic castration-resistant prostate cancer, advice regarding intermittent versus continuous androgen deprivation therapy, and consideration of whether to treat the primary tumor in men diagnosed with de novo metastatic prostate cancer.
We used probe combinations that included the androgen receptor (AR) and MYC genes for FISH analysis of CTC samples collected from 77 men with castration-resistant metastatic prostate cancer.
As second-generation androgen receptor antagonists have been increasingly used for treatment of castration-resistant stage metastatic prostate cancer, new onset of symptomatic epidural lipomatosis should be considered as a possible differential diagnosis, especially because the urinary symptoms of cauda equina compression may be improperly attributed to the primary prostate neoplasm.
Comprehensive proteomic profiling identifies the androgen receptor axis and other signaling pathways as targets of microRNAs suppressed in metastatic prostate cancer.
Two features of the progression from organ-confined to metastatic prostate cancer are dysregulation of the androgen receptor (AR) and a decrease in insulin-like growth factor-type-I receptor (IGF-IR) expression.
Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC).
A novel AR signaling pathway that induces microRNA-1 (miR-1) to suppress metastatic prostate cancer was recently demonstrated (AR-miR-1 signaling axis), and its regulation of Wnt signaling was explored in the current study.
CAG polymorphic repeat length in androgen receptor gene combined with pretreatment serum testosterone level as prognostic factor in patients with metastatic prostate cancer.
We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study.
The Detection of Androgen Receptor Splice Variant 7 in Plasma-derived Exosomal RNA Strongly Predicts Resistance to Hormonal Therapy in Metastatic Prostate Cancer Patients.
The AR amplification frequencies were 45 and 35 % in local recurrent castration-resistant prostate cancer and distant metastatic prostate cancer, respectively.