KLK3 (Kallikrein-related peptidase 3)

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.

Trichodermamide B targets catalase while mediating crosstalk between the catalase axis and the AR signalling axis to induce oxidative stress and apoptosis in prostate cancer cells. Its efficacy in both in vitro and in vivo models underscore its viability as a novel drug candidate for prostate cancer treatment.

We provide the first systematic single-cell atlas of UPR heterogeneity in PCa and develop a clinically translatable UPRRS prognostic model. IFRD1, a key driver, emerges as a dual diagnostic and therapeutic target, offering both theoretical and experimental foundations for precision stratification and individualized management of PCa.

Collectively, our findings establish ZNF711 as a critical regulator of ENZR that promotes resistance by dually modulating the AR signaling pathway via transcriptional activation and epigenetic demethylation. Targeting the ZNF711-AR axis represents a novel therapeutic strategy to overcome ENZR in prostate cancer.

Immunohistochemical PSA and Ki-67 expression provide practical prognostic information for patients with metastatic castration-sensitive prostate cancer. Combined assessment with EOD ≥ 3 identifies a high-risk subgroup with unfavorable clinical outcomes.

By inhibition with the recombinant protease inhibitor MDPK67b targeting KLK2 and other trypsin-like KLKs including KLK4 and KLK14, we investigated the antitumor response and the influence on AR downstream target genes with MDPK67b in PCa cell lines in vitro...Therefore, inhibition of KLKs represents a promising and AR-independent approach to treat advanced and CRPCa. ClinicalTrials.gov ID: NCT04644770.

To date, the successful implementation of artificial intelligence (AI) in the biosciences has significantly contributed to drug discovery. Our review focuses on state-of-the-art strategies and techniques in the context of KLK targets.

Future studies should focus on in vivo models to validate these effects and explore the underlying mechanisms, which may open new therapies for PCa. STATEMENT OF IMPLICATION: AdipoRon decreases prostate cancer cell growth.

These data show that KLK3 SNPs disrupt dynamic communication of the key loops required for proteolytic activity of PSA, which may explain the association of these SNPs with prostate cancer risk and/or progression.

Druggability analyses nominated several potential drug targets for PCa, such as HSPB1, RRM2B, and PSCA. Our findings reveal novel risk loci and candidate protein biomarkers, providing new etiological insights and potential avenues for PCa early detection and therapy.

Additionally, the hormone-mediated upregulation and AR antagonist-driven downregulation of PSA gene expression were respectively attenuated and enhanced in PACT KO cells. Taken together, these data support a pro-proliferative role for PACT in PCa, and siRNA therapeutic targeting of PACT, or downregulated genes with PACT KO, could represent a new therapeutic approach.

Mice received DMSO, abiraterone, or MPT1A160 intraperitoneal injections twice per week...Furthermore, several MPT1A160-suppressed genes exhibited high mutation frequencies in prostate cancer, suggesting their potential role in therapy resistance. MPT1A160 exhibits potent anti-tumor effects by targeting both androgen biosynthesis and epigenetic regulation, offering a novel dual inhibition strategy for overcoming treatment resistance in prostate cancer.