Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens.
Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)-resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor-positive and AI-resistant disease in this phase II, single-arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage.
Mechanistically, KIF4A and AR form an auto-regulatory positive feedback loop in prostate cancer: KIF4A binds AR and AR-V7 and prevents CHIP-mediated AR and AR-V7 degradation; AR binds the promoter region of KIF4A and activates its transcription.
Although AR plays a key role, it is likely that other molecular pathways also contribute to PC, making it essential to identify and develop drugs against novel targets.
The heat shock protein 70 inhibitor VER155008 suppresses the expression of HSP27, HOP and HSP90β and the androgen receptor, induces apoptosis, and attenuates prostate cancer cell growth.
The function of NE cells in PCa remains poorly understood, and one important characteristic of these cells is their lack of expression of AR and resistance to hormonal therapy.
5α-Dihydrotestosterone (5α-DHT) possesses a great affinity for the androgen receptor (AR), and its binding to AR promotes the proliferation of prostate cancer (PC) cells in androgen-dependent PC.
Therefore, inhibiting WNT/β-catenin signalling by limiting WNT secretion in concert with AR inhibition may be useful for treating prostate cancers with alterations in WNT pathway genes.
Mechanistically, we also showed that circZMIZ1 could increase the expression of androgen receptor (AR) and androgen receptor splice variant 7 (AR-V7), which may be partly contributed to the occurrence and development of prostate cancer.
Here we found that adding R-2HG or the mutant IDH1 R132H could promote PCa cell invasion in androgen receptor (AR)-negative PC3 cells or suppressing the AR in AR-positive C4-2 cells.
In this review, we will summarize our current knowledge on the roles of JNK in the apoptosis, proliferation, migration and DNA repair as well as dissect the relationships between JNK and androgen receptor in prostate cancer.
Our results indicate that PCa family history may be positively associated with PCa in all ERG and PTEN subtypes, suggesting a role of genetic susceptibility in their development.
Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2-AR axis and provide novel evidence towards a strategy against prostate cancer.
The recent availability of selective AR inhibitors (e.g. bicalutamide, enzalutamide, apalutamide) approved for the treatment of prostate cancer has opened up the possibility to use them in BC patients whose tumors express AR.
Together, these results provide the first detailed mechanism of how the AR can differentially alter PCa and BCa metastasis; thus, targeting the newly identified AR-miR-525-5p-SLPI axis may help suppress metastasis.
Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, interleukin-1 (IL-1), represses AR messenger RNA (mRNA) levels and activity in AR-positive (AR<sup>+</sup> ) PCa cell lines concomitant with the upregulation of prosurvival biomolecules.