LRRC8D downregulation was accompanied by suppression of swelling-activated VRAC currents, increased synaptophysin (SYP) expression, decreased cisplatin sensitivity, and neurosecretory remodeling...Consistent alterations in LRRC8D and SYP expression were also observed in enzalutamide-resistant patient-derived organoids...Functional analyses further showed that CAV-1 acted upstream of LRRC8D, and LRRC8D negatively regulated STAT3 activation. Together, these findings indicate that LRRC8D influences PCa phenotype and platinum responsiveness and implicate a regulatory axis involving LRRC8D and CAV-1/STAT3 signaling in NE-associated features of advanced PCa.

P2, N=60, Active, not recruiting, University of Wisconsin, Madison | Trial completion date: Oct 2026 --> Mar 2027

P2, N=50, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

Phenotypic characterisation was conducted using immunofluorescence staining for molecular markers of plasticity and stemness, and drug resistance was assessed with doxorubicin and enzalutamide, the latter chosen for its emerging relevance in targeting stem-like cancer cell populations. The 3D matrices reproduced the mechanical regulation observed in 2D, providing a physiologically relevant platform for high-throughput investigation of biomechanics-driven cancer progression. These findings highlight the role of matrix stiffness in driving breast cancer phenotypic heterogeneity and support the application of microengineered synthetic matrices for studying metastasis and drug resistance.

Sixteen-week-old mice underwent surgical and chemical castration (10 mg/Kg enzalutamide), alone or in combination with JPE (5.8 g/Kg)...Mechanistically, JPE-induced effects in castrated mice involved decrease of AR protein expression as well as ERβ beneficial actions, which included a putative stimulation of TGF-β tumor-suppressive actions. In conclusion, JPE prevented the progression of poorly differentiated tumors with CRPC traits in the TRAMP model by hampering EMT and modulating steroid hormone and TGF-β signaling.

The results indicate that NUSAP1 enhanced prostate cancer ENZ resistance through activation of the Wnt/β-Catenin-AR/AR-V7 signalling pathway. Targeting NUSAP1 could offer a potential therapeutic approach to address ENZ resistance in CRPC.

Direct AR antagonism enhances functional PSMA availability and increases short-term uptake of PSMA-targeted radioligands in AR-positive prostate cancer models. These findings provide mechanistic support for AR-mediated modulation of PSMA-targeted radioligand delivery and warrant further translational investigation.

The initial intensified systemic regimen is the doublet therapy of Darolutamide (600 mg orally twice daily) and goserelin (10.8 mg administered subcutaneously every 3 months). During 20 months of follow-up, the patient maintained an undetectable PSA, and had no radiographic evidence of disease relapse with well treatment tolerance. This case suggests that darolutamide plus ADT, administered as a tailored perioperative intensified systemic strategy, may induce a rapid and profound PSA response and may be associated with pCR in selected patients with very high-risk LAPC, while further investigation is warranted.

P2, N=111, Completed, Alliance Foundation Trials, LLC. | Active, not recruiting --> Completed | Trial completion date: Aug 2026 --> May 2026

Study findings will be disseminated through peer-reviewed publications and conference presentations. 2025-520482-52-03 (https://euclinicaltrials.eu/ctis-public/view/2025-520482-52-03?lang=en, protocol nr 6.0).

P=N/A, N=100, Active, not recruiting, Bayer | Trial primary completion date: Jul 2026 --> Mar 2026

P2, N=254, Not yet recruiting, West China Hospital