Prostate Cancer

P1, N=28, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

Furthermore, our findings show that the dual-targeting agents JQ-1 and CX-6258-focused on FOSL1/AP-1 and PIM kinases, respectively-effectively suppress both the progenitor properties and the growth of mouse and human DNPC surrogates in vitro and in vivo. Thus, early eradication of castration-tolerant Club-like cells presents a promising therapeutic strategy to mitigate prostate cancer progression toward CRPC.

The anti-hyperproliferation and the anti-inflammatory effects of DHM were attributed to the attenuation of the expression of PCNA, procaspase-3, iNOS, TLR-4, and IL-1β in both the prostate and seminal vesicle tissues. DHM has potential protective effects against testosterone-induced BPH model via downregulation of inflammatory mediators, restoration of oxidative balance, and induction of cell apoptosis.

This study identifies a mechanism of OH2-induced PD-L1 expression in PCa and provides a versatile, targeted delivery platform that enables effective intravenous viro-immunotherapy, overcoming key translational barriers.

Based on the clinical candidate Opevesostat, two series of 23 new compounds were designed and synthesized using a 4H-pyran-4-one core to explore structure-activity relationships at the C2 and C6 positions.Compound II-4 exhibited potent inhibitory activity (95.2% at 100 nM; IC₅₀ = 26.7 nM), comparable to Opevesostat (IC₅₀ = 20.4 nM). Importantly, II-4 showed superior selectivity against CYP1A2, 2C9, and 2D6 (2- to 4-fold improvement), attributed to hydrophobic interactions between its C6 methyl group and Ile 84.These results highlight II-4 as a promising lead compound with optimized activity and selectivity, providing valuable insights for overcoming resistance in prostate cancer therapy.

P=N/A, N=230, Active, not recruiting, Boston Scientific Corporation | Recruiting --> Active, not recruiting

ImmunoPET identified &lsqb;89Zr]Zr-DFO-TDI-Y-010 as the top-performing diagnostic tracer, with excellent in vivo biodistribution and tumor-to-background-organ ratios consistently >4. Therapeutic studies with &lsqb;177Lu]Lu-CHX-A"-DTPA-TDI-Y-010 demonstrated strong antitumor effects, significantly improving (P <0.05) overall survival compared with the benchmark clone &lsqb;177Lu]Lu-CHX-A"-DTPA-SC16.56 in two SCLC tumor models (NCI-H82 and Lu149) and achieving comparable overall survival in a NEPC tumor model.

This study revealed that IL1RA low expression is associated with PCa progression. Our finding has great clinical and translational significance. The potential clinical application of IL1RA as a therapeutic target for PCa requires further investigation.

Beyond the intracellular context, we discuss how proteostatic imbalances drive the senescence-associated secretory phenotype (SASP) to remodel the tumor microenvironment. Finally, we assess emerging therapeutic strategies, arguing that precision modulation of specific proteostasis nodes-such as distinct E3/DUBs or CMA pathways-represents a promising frontier to overcome castration-resistant prostate cancer (CRPC).

In addition, the in vivo efficacy was also assessed in xenograft mouse models of non-CNS tumors, where PSMA CAR T cell treatment resulted in significant tumor regression and robust accumulation of CAR T cells within the tumor microenvironment. Together, these findings establish PSMA as a promising surface antigen beyond prostate cancer and provide preclinical evidence supporting the development of PSMA-directed therapies for this highly lethal pediatric cancer.

Interestingly, several prostate cancer-associated genes were also associated with breast, cervical, and lung cancers. These findings suggest potential biological mechanisms linking immune cells to cancer development and progression, highlighting the complex role of the immune system in 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.