While PTEN inactivation leads to PC, it is not sufficient for metastasis, the loss of PTEN concurrently with the inactivation of both TP53 and RB1 empower lineage plasticity in PC cells, which substantially promotes PC metastasis and the conversion to PC adenocarcinoma to neuroendocrine PC (NEPC), demonstrating the essential function of TP53 and RB1 in the suppression of PCSCs.
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.
The findings on the roles of NRs in prostate cancer thus far have shown that several NRs such as vitamin D receptor, estrogen receptor β, and mineralocorticoid receptor play antioncogenic roles, while other NRs such as peroxisome proliferator-activated receptor γ and estrogen receptor α as well as androgen receptor play oncogenic roles.
Biochemical recurrence, distant metastasis, and the final scores of EphA3 and AR expression were significantly correlated with the prognosis of PCa (P < 0.05).
Ablation of androgen receptor (AR) signaling by androgen deprivation is the goal of the first line of therapy for prostate cancer that initially results in cancer regression.
PTEN (Phosphatase and Tensin Homolog) mutant is the top common mutated genes in prostate cancer, which makes it a promising biomarker in future individualized treatment.
These novel findings indicated that 4-1BBL might mediate prostate cancer progression to castration-resistant prostate cancer via enhancing expression and function of AR.
We uncovered a novel interplay between AR and PBK that results in increased AR and ARVs expression that executes AR-mediated growth and progression of PrCa, with implications for the development of PBK inhibitors for the treatment of aggressive PrCa.
Overall, our study demonstrates that <i>IDH1</i> expression is associated with prostate cancer progression, that AR signaling integrates one of the first transcriptional mechanisms shown to regulate <i>IDH1</i>, and that AR reprograms prostate cancer cell metabolism by selectively inducing extra-mitochondrial IDH activity.
Ipatasertib combined with abiraterone in PTEN-null prostate cancer improved progression-free survival in a randomized phase II study of patients with metastatic castration-resistant prostate cancer (mCRPC), providing clinical evidence of reciprocal activation between the Akt and androgen receptor (AR) pathways.
Although radiosensitization mechanisms are known to be mediated through androgen receptor activity, this project aims to uncover the detailed DNA damage repair factors influenced by enzalutamide using multiple models of androgen-sensitive (LNCaP) and castration-resistant human prostate cancer (22Rv1 and DU145).
PTEN loss was significantly (P < 0.05) associated with increasing GG, poorly formed glands (74% of total cases with loss vs 49% of intact), and three well-validated unfavorable pathological features: intraductal carcinoma of the prostate (IDC-P) (69% of total cases with loss vs 12% of intact), cribriform Gleason pattern 4 (38% of total cases with loss vs 10% of intact) and stromogenic PCa (23% of total cases with loss vs 6% of intact).