Selectively blocking MDM2-mediated activity in combination with androgen/AR-targeted therapy may offer a novel strategy for eliminating AR<sup>-</sup> CSCs in addition to the bulk of AR<sup>+</sup> prostate cancer cells, decreasing metastatic tumor burden and inhibiting the emergence of therapeutic resistance.<b>Significance:</b> These findings provide a novel mechanistic aspect of prostate cancer cell stemness that advances our understanding of the diverse transcriptional activity that bypasses AR in contributing to therapeutic resistance, tumor progression, and metastasis.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/79/6/1124/F1.large.jpg.
Notably, the pre-treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti-androgen therapy, showed AR expression and no AR splice variants.
Simvastatin delays castration‑resistant prostate cancer metastasis and androgen receptor antagonist resistance by regulating the expression of caveolin‑1.
However, AR expression revealed a significant correlation with tumor size (p=0.026), tumor differentiation (p=0.047), American Joint Committee on Cancer (AJCC) staging (p=0.043), lymph node positivity (p=0.018), lymphovascular invasion (p=0.018), and distant metastasis (p=0.049).
Current PC therapies prevalently target the functions of androgen receptor (AR) and may only be effective within short time periods, beyond which the majority of PC patients progress to castration-resistant PC (CRPC) and metastatic disease.
Body mass index (P = .023) and DACH1 (P = .034) were correlated with MBC prognosis, whereas the expression of AR (P = .049), SIX1 (P = .048), surgery (P < .001), and chemotherapy (P = .001) were important for FBC in addition to already known factors: tumor size and location, TNM stage (lymph nodes and organ metastasis), radiotherapy, and ER and human epidermalgrowth factor receptor-2 (HER2) expression.
Greater knowledge about the structural and functional biology of the androgen receptor in prostate cancer will facilitate further discovery and development of further improved antiandrogens with enhanced clinical activity in patients with advanced metastatic disease.
As PCa is hormone dependent, blockade of the androgen receptor (AR) signaling is an effective therapeutic strategy for men with advanced metastatic disease.
The signaling cross-talk between transforming growth factor-β and androgen receptor signaling will be interrogated as a new therapeutic platform for the development of combination strategies to impair prostate cancer metastasis.
We sought to identify the plausible stemness factor that determines the "molecular signature" of prostate cancer (PCa) cells derived from different metastases (PC3, PCa2b, LNCaP, and DU145) and whether androgen receptor (AR) influences the maintenance of stemness features.
Our findings not only provide new insights into the mechanisms of lncRNA in regulating AR but also suggest ARNILA as an alternative therapeutic target to suppress metastasis of TNBC patients.
We did not find any GATA3 or AR expression in the metastases from endometrial or salivary gland carcinomas, while GATA3 expression was seen in the majority of metastases from urothelial or breast carcinomas.
Recent genome-wide analysis of prostate cancer metastases illustrate the importance of the Wnt/β-catenin pathway in prostate cancer and compel us to reexamine the interaction of the AR and Wnt/β-catenin signaling pathways.
We found a good concordance of AR expression between primary tumor and metastasis, but the variability remains high between the two types of specimens, regardless of the variation in sampling time.
<b>Introduction</b>: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis.