AR positive

Mechanistically, while stimulation with the AR-agonist R1881 is sufficient to induce nuclear translocation of AR in AR+ TNBC cells, AR inhibition with enzalutamide, apalutamide, or darolutamide blocked AR nuclear translocation. These findings suggest that AR-mediated radioresistance is at least partially due to downstream MAPK/ERK signaling. Together this work builds on the mechanistic understanding of AR-mediated radioresistance in AR+ TNBC which may expose vulnerabilities in resistance to combination treatment with AR inhibition and RT.

Importantly, oral administration of 26 and 28 elicited significant in vivo antitumor efficacy in a 22Rv1 xenograft model, with no detectable systemic toxicity observed in treated mice. These results identify 26 and 28 as promising orally bioavailable LRH-1 antagonists, validating them as attractive lead molecules for further structural optimization and development for castration-resistant prostate cancer (CRPC) therapy.

Consequently, SNHG18 deficiency fosters an immunosuppressive TME and promotes PCa BM. SNHG18 expression may serve as a predictive biomarker for ICB response, offering a novel strategy to overcome immunotherapy resistance in PCa BM.

Central determination of AR showed significant enrichment in HER2-low compared with HER2-0 mTNBC (mean: 33.7% vs. 21.4%, p = 0.038), whereas no significant immunological differences were observed. HER2-low/AR-positive patients trended towards longer overall survival, highlighting the potential relevance of these biomarkers.

In Cap-R cells, the combination of Cap and WH23 significantly induced apoptosis, demonstrating a synergistic anticancer effect. These findings establish WH23 as a dual-acting compound targeting both androgen biosynthesis and AR signaling, with potential to overcome AKT inhibitor resistance in LAR TNBC.

Pharmacokinetic and pharmacodynamic analyses further supported TaxO's favorable safety profile. These findings highlight TaxO as a promising plant-based therapeutic candidate for targeting AR-driven prostate cancer, warranting further clinical investigation.

AR is a promising prognostic marker and therapeutic target in TNBC, despite its low prevalence (15.4%). To confirm these results and standardize AR positive levels, larger, multi-center studies are required.

Treatment with enzalutamide, an antiandrogen, substantially inhibited patient-derived xenografts growth and demonstrated additive antitumor effects when combined with chemotherapy in AR-positive models...AR expression correlated with poorer overall survival, with statistical significance noted in the full cohort and particularly in male patients. This study suggests that AR may promote metastatic NPC progression via the TTF-1/EGFR signaling pathway and interact with EBV to influence disease behavior, especially in males.

Immunostain for androgen receptor was strongly and diffusely positive in the primary tumor and in the nodal metastasis, which together with focal staining for NKX3.1 were suggestive of primary prostatic origin and invited consideration of androgen deprivation therapy. This report highlights a rare prostatic Ewing-family sarcoma harboring an EWSR1::FEV fusion and immunophenotypic features that mimic a neuroendocrine carcinoma.

Although significance was observed only in certain subgroups, AR status may have clinical value and warrants further investigation using standardised assessment methods. CRD42023447385.

In summary, an optimized one-pot, two-step synthesis of [18F]FPIA on a vial-based automated synthesizer was successful and a seamless transition into a GMP facility is reported, enabling a streamlined transition to clinical production. Furthermore, we have demonstrated the use of [18F]FPIA for noninvasive metabolic imaging in prostate cancer and its potential to distinguish between different prostate cancer subtypes.

Moreover, immunohistochemical analysis of ex vivo- irradiated, patient - derived PCa tissues from patients with newly diagnosed high - Gleason score prostate cancer undergoing prostatectomy further demonstrated that radiation-induced autophagy supports the survival of high-grade AR-positive tumor cells. Collectively, our findings reveal that AR promotes radioresistance in PCa by enhancing both DNA repair and autophagy.