P4, N=20, Not yet recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

While next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide and abiraterone, have revolutionized CRPC treatment, resistance to these therapies remains a significant challenge, rendering the disease incurable. Compelling evidence further suggests that combining PLK1 inhibition with paclitaxel could serve as an effective therapeutic strategy to overcome resistance in CRPC by targeting microtubule dynamics. This review examines the mechanistic role and broader implications of PLK1 in CRPC treatment, offering valuable insights into potential combination therapies to improve efficacy and patient outcomes.

P=N/A, N=1067, Not yet recruiting, Novartis Pharmaceuticals

However, the impact of AR splice-variants on responses to bicalutamide (Bica) and enzalutamide (Enza) is not well understood across various breast cancer forms. Total AR protein alone is insufficient for patient stratification. These insights support the inclusion of AR splice-variant analysis in biomarker-based strategies to enable precise AR-targeted therapies in breast cancer.

P2, N=80, Recruiting, Cedars-Sinai Medical Center | Not yet recruiting --> Recruiting | Initiation date: Apr 2026 --> Aug 2026

P3, N=27, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Jun 2026 --> Sep 2026

P=N/A, N=805, Active, not recruiting, Bayer | Trial primary completion date: Dec 2026 --> Jul 2026

P=N/A, N=3000, Recruiting, Bayer

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.