Integrating multi-omics proteomic approaches in deciphering the tumor microenvironment and therapeutic resistance mechanisms in prostate cancer.

Prostate cancer (PCa) is one of the main causes of cancer-related mortality. The tumor microenvironment (TME) and the development of drug resistance pose significant challenges to effective cancer therapy. This review explores the integration of multi-omics proteomic approaches to decipher the complex interactions within the TME and the mechanisms driving resistance in PCa. We discuss how proteomics and genomics, transcriptomics, and metabolomics enhance our understanding of the molecular drivers of cancer progression, immune evasion, and treatment failure. Emphasis is placed on recent advances in proteomic profiling of the TME, including extracellular matrix components and immune regulators, and how single-cell proteomics provides insights into tumor heterogeneity. We also highlight the multi-omics role in identifying post-translational modifications and kinase pathways contributing to therapeutic resistance, and its implications for biomarker discovery and personalized medicine. The review concludes by addressing the clinical potential of multi-omics approaches and their future role in improving outcomes for prostate cancer patients.