AR positive

The HOXB13/SMARCD2 interaction alters chromatin accessibility at HOXB13-binding sites, causing increased proliferation in AR-negative PCa. Overall, this work demonstrates a distinct mechanism of action for HOXB13 and highlights its critical role in AR-negative castration-resistant PCa.

No ABC showed AR positivity, while this was observed in rare cells (IRS 1-2) in 30.8%, 16.6%, and 37.5% of TSCs, EPTs, and ABHs, respectively. HoxB13 can be a useful and reliable marker for identification of TSPs, EPTs and ABCs.

Interestingly, RSGs and the AR have non-genomic interactions via membrane-localized AR (mAR) not affected by AR inhibitors. Drugs that target RSGs are needed along with AR inhibitors to prevent mPCa progression.

P2, N=88, Active, not recruiting, Fudan University | Recruiting --> Active, not recruiting

AC is characterized by distinct metabolic reprogramming, with preferential upregulation of peroxisomal β-oxidation rather than mitochondrial pathways. These metabolic features are accompanied by a high prevalence of activating PIK3CA mutations, suggesting a link between genomic alterations and metabolic phenotype. These findings provide new insights into the pathobiology of AC and may assist in its histopathological differentiation from other breast cancer subtypes.

Moreover, pharmacological GRPR inhibitor represses FAM135A expression via MED15 activation. Together, we unveil FAM135A as an oncodriver and biomarker of PCa perineural invasion, and provide a novel strategy for PCa innervation therapeutics.

Furthermore, we explored a novel combination therapy involving the histone methyltransferase inhibitor MI-503 and enzalutamide in AR-positive and AR splice variant-positive cell lines. Our results confirmed the synergistic therapeutic effects of this combination, which can continue to inhibit the AR signaling pathway during the CRPC stage, thereby delaying disease progression. Taken together, our findings elucidate a critical KMT2D/G3BP1/SPOP/AR regulatory axis in prostate cancer progression and propose that targeted inhibition of histone methylation in combination with anti-androgen therapy represents a promising strategy for the management of advanced prostate cancer.

P2, N=51, Recruiting, Vandana Abramson | Not yet recruiting --> Recruiting

Our study revealed that BAP18, which acts as a novel AR corepressor, is involved in AR-positive TNBC progression, suggesting that BAP18 could be a potential therapeutic target for AR-positive TNBC patients.

Drug screening with UM spheroids revealed that prazosin and doxazosin dose-dependently reduced viability, whereas terazosin, alfuzosin, silodosin, tamsulosin, and phenoxybenzamine were found to be inefficient. This suggests a tumor-preventive effect through the blockade of α1A-AR. The present study highlights the responses of UM spheroids to α-AR antagonists and demonstrates that prazosin, doxazosin, or RS17053 may be a treatment option for preventing UM tumor recurrence or metastasis.

Additionally, methylation patterns of AR co-regulators located on the X chromosome suggest epigenetic regulation of AR signaling in gliomas. The findings reveal distinct AR pathway activation patterns in adult-type diffuse gliomas, particularly IDH-wildtype GBMs, suggesting that further exploration of antiandrogen therapies is warranted.

In multicellular tumor spheroids, 2 disrupted spheroid integrity (IC50 = 14 μM). These findings indicate the potential of A-ring substituted androgen-ferrocene conjugates as antiproliferative agents for hormone-dependent cancers, with 2 emerging as a promising candidate that surpasses cisplatin in potency and appears to act through a distinct mechanism.