SPOP (Speckle Type BTB/POZ Protein)

Hence, a deeper investigation into the molecular mechanisms of SPOP in prostate cancer will provide novel insights into its physiological function in oncogenesis and drug development. In this review, we summarize SPOP's tumor suppressor functions and structural features, upstream regulatory mechanisms, and SPOP-targeting therapeutic strategies in prostate cancer.

In this exploratory analysis, we found that Black men have improved survival in the first line mCRPC setting with ARPI therapy, but that SPOP mutations do not explain these differential outcomes despite improved short term PSA declines. Thus, other factors may explain the disparity in outcomes we confirmed in men with CRPC.

uncover a novel SPOP-USP7-TREX1 axis that controls cytosolic DNA clearance after DNA damage, thereby gating tumor-cell-intrinsic cyclic GMP-AMP synthase (cGAS)-STING activation and response to radioimmunotherapy. Compellingly, targeting USP7 and TREX1 might sharpen patient selection and combination strategies.

PPFIA2 is an unfavorable prognostic biomarker for localized PCa. Its oncogene effect highlights its potential for risk stratification and targeted therapy.

Integrating multi-omics technologies, liquid biopsy platforms, and AI-assisted imaging offers new opportunities for dynamic disease monitoring and biology-driven treatment selection. By consolidating current clinical practices with emerging experimental directions, this review provides clinicians and researchers with a comprehensive perspective on the evolving landscape of precision medicine in prostate cancer and highlights future opportunities to improve patient outcomes.

Hence, our findings reveal a pivotal role of the SPOP/USP2 axis in regulating CD47 protein stability and advocate for combining USP2 inhibitors with anti-PD-1 immunotherapy to combat cancer.

Finally, we demonstrate that both SPOP-F102C and SPOP-F133L support targeted protein degradation in an engineered cellular system. These findings define the degradative capacities of SPOP mutants and highlight opportunities to repurpose these variants as mutant-selective E3 ligases for therapeutic applications.

Furthermore, USP7 inhibitors reduce TREX1 levels and restore immune responses following radiation. These findings elucidate the mechanisms linking DNA damage to immune activation and highlight USP7 inhibitors as potential enhancers of radioimmunotherapy.

P2, N=8, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=30 --> 8 | Trial completion date: Mar 2027 --> Mar 2026 | Trial primary completion date: Mar 2027 --> Mar 2026

The MLCS is a scoring tool to assist in timing and selecting therapeutic combinations of ARPI with TREM2 or CSF1R blockade, PARPi with STING modulation, and ARPI with anti-CD47 therapy. Integrating mechanistic and translational data provides a foundation for biomarker-guided regimens capable of converting prostate cancer from an immune-cold disease to an immune-responsive state.

Ferroptosis-induced immunogenic cell death enables synergy with checkpoint inhibitors, potentially transforming immunologically "cold" prostate tumors. This review establishes ferroptosis targeting as a precision medicine paradigm exploiting the tension between the oxidative requirements of cancer cells and their evolved, yet architecturally vulnerable, defense systems, providing a framework for stage-specific, biomarker-guided interventions.