Castration-Resistant Prostate Cancer

The combined suppression of PI3K/AKT and KMT2D reduced cell proliferation in prostate cancer cells and patient-derived organoids in both CRPC-AR and CRPC-SCL subtypes. Altogether, these results unveil KMT2D as a major mediator of the epigenetic landscape in subtype-specific CRPC, contributing to tumor growth and therapeutic response.

Together, these therapies form the basis of emerging strategies to more effectively suppress AR activity in CRPC. This review discusses AR-activating mechanisms, the mechanisms of action of these agents, their clinical development status, and their potential to reshape future treatment paradigms in CRPC.

Lutetium-177-PSMA-617 has become the standard radioligand therapy for metastatic castration-resistant prostate cancer, whereas alpha-emitting agents remain under clinical investigation...Integrative models combining imaging, genomic, and liquid biopsy data pave the way toward precision oncology and personalized therapeutic decision-making. Advances in imaging and theragnostics are reshaping prostate cancer management, bridging the gap between molecular biology and clinical practice to enable precision oncology.

Our findings demonstrate that SBFI-1143 significantly alters the transcriptomic landscape of prostate cancer and may serve as a potentially effective therapeutic option for this disease.

P3, N=800, Not yet recruiting, Janssen Research & Development, LLC | Trial completion date: Jun 2030 --> Jun 2029

CAS significantly enhanced ABI's cytotoxic efficacy in 22Rv1 cells, as evidenced by synergistic interactions (CI: 0.31-0.71); however, no such synergy was observed in LNCaP cells or with enzalutamide. Docking and molecular dynamics simulations indicated a stable CAS-AKR1C3 interaction, characterized by crucial hydrogen bonding and aromatic stacking within the active site. These results suggest that CAS is a promising chemosensitizer targeting AKR1C3 to overcome ABI resistance in CRPC.

These findings suggest that the circulating 3LS is not just a prognostic biomarker, but an actionable signature reflecting changes in PC biology. The plasma lipid milieu identified by the 3LS drives a pro-survival phenotype by modifying lipid metabolism and upregulating ceramide/S1P signalling. The study provides the biological rationale to target ceramide-S1P signalling in patients, who are 3LS-positive.

P1/2, N=39, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Oct 2029 --> Jan 2030 | Trial primary completion date: Oct 2027 --> Jan 2028

Given the use of sipuleucel-T as a standard of care backbone, there is emerging interest in combining it with other immunotherapies, hormonal therapies, or chemotherapies to improve its clinical efficacy. This review summarizes past experiences and current knowledge of combining sipuleucel-T with other treatments and explores future approaches to enhance such combinatorial strategies.

P1/2, N=174, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

PATIENT SUMMARY: Our mini review looks at the evidence for drugs called PARP inhibitors for metastatic prostate cancer that does not respond to standard hormone therapy (mCRPC for short). Combination treatment with a PARP inhibitor and another type of drug called an androgen receptor pathway inhibitor is approved in Europe for all patients with mCRPC, but those who are most likely to benefit have mutations in genes that are involved in a type of DNA repair.

This review clarifies how MAO influence PCa progression by regulating the "tumor-stroma-immune" interaction network, elucidate the impact of MAO on CD8+ T-cell infiltration and tumor-associated macrophages (TAMs) polarization in the TME, and proposes that precision targeting of MAO offers a stage- and cell-type-spanning strategy to surmount immunotherapy resistance in PCa. It provides a theoretical basis for developing intervention strategies based on MAO inhibitor to achieve effective immunotherapy for PCa.