We performed integrative analysis for 3 sets of prostate cancer (PCa) genomic data, and found that BMI1 and androgen receptor (AR) were positively correlated, suggesting that AR might regulate BMI1.
Both hormone-sensitive and castration- and enzalutamide-resistant prostate cancers (PCa) depend on the ternary complex factor (TCF) protein ELK1 to serve as a tethering protein for the androgen receptor (AR) to activate a critical set of growth genes.
The major topic areas discussed at this year's meeting included (a) new insights into prostate cancer biology and treatment; (b) approaches for accelerating precision medicine for prostate cancer; (c) prostate-specific membrane antigen-targeted therapy and imaging for prostate cancer; (d) updates on Poly (ADP-ribose) polymerase (PARP)-inhibitor clinical trial results; (e) the biology and role of prostate cancer stem cells; (f) new approaches for targeting the androgen receptor and other steroid hormone receptor pathways; (g) racial disparities in prostate cancer treatment and outcomes; (h) the role of the nervous system in prostate cancer development and progression; (i) the role of the WNT signaling pathway in normal prostate and prostate cancer biology; (j) novel immunotherapy approaches; and (k) the ecology of prostate cancer.
ARD-69 is capable of reducing the AR protein level by >95% in these prostate cancer cell lines and effectively suppressing AR-regulated gene expression.
Despite the AR being one of the most studied and attended targets in cancer, those gain-of-function mutations in the receptor remain a significant challenge for the development of PCa therapies.
Many genes exhibit evidence for allele-specific transcriptional activation by PrCa master-regulators (including androgen receptor) in Position Weight Matrix, Chip-Seq, and Hi-C experimental data, suggesting common regulatory mechanisms for the associated genes.
Collectively, this work provides a potential lead compound for anticancer agent development related to prostate cancer therapy, and took a step forward towards the development of novel and improved AR antagonists.
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.
In agreement, bioinformatics analysis of clinical RNA sequencing data involving GSEA indicated a strong correlation between AR and EZH2 gene expression during PCa progression.
Since AR remains a driver of PCa in advanced disease, strategies targeting both lipid metabolism and AR are starting to emerge, providing new opportunities to re-sensitize tumors to endocrine therapies with lipid metabolic approaches.
The goal was to characterize androgen receptor gene (<i>AR</i>) amplifications and mutations detected in ctDNA from patients with PCa and to further understand the somatic genetic heterogeneity of advanced prostate cancer.
Darolutamide (NUBEQA™) is a structurally distinct non-steroidal androgen receptor antagonist being developed by Orion and Bayer as a treatment for prostate cancer.