Abstract
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, PTEN loss, BRCA1/BRCA2 mutations, ATM alterations, SPOP 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 CDK12-altered tumors, targeted interventions for SPOP-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.