Precision Medicine in Prostate Cancer with a Focus on Emerging Therapeutic Strategies

Precision medicine has reshaped the clinical management of prostate cancer by integrating comprehensive genomic profiling, biomarker-driven patient stratification, and the development of molecularly targeted therapeutics. Advances in next-generation sequencing have uncovered diverse genomic alterations-including homologous recombination repair defects, MSI-H/MMRd, <i>PTEN</i> loss, <i>BRCA1/BRCA2</i> mutations, <i>ATM</i> alterations, <i>SPOP</i> mutations, and molecular hallmarks of neuroendocrine differentiation-that now inform individualized treatment decisions. This review synthesizes established clinical evidence with emerging translational insights to provide an updated and forward-looking overview of precision oncology in prostate cancer. Landmark trials of PARP inhibitors and PSMA-targeted radioligand therapy have redefined treatment standards for biomarker-selected patients. Concurrently, efforts to optimize immune checkpoint inhibition, AKT pathway targeting, and rational combinations with androgen receptor pathway inhibitors continue to expand therapeutic possibilities. Rapidly evolving investigational strategies-including bipolar androgen therapy (BAT), immunotherapeutic approaches for <i>CDK12</i>-altered tumors, targeted interventions for <i>SPOP</i>-mutated cancers, and epigenetic modulation such as EZH2 inhibition for neuroendocrine prostate cancer-further illuminate mechanisms of tumor evolution, lineage plasticity, and treatment resistance. 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.