Work

The role of the p53 signaling pathway in prostate cancer

Year: 2026

Type: review

Abstract: The p53 signaling pathway is pivotal for maintaining genomic stability and regulating cell fate, playing a critical role in the initiation, progression, and treatment resistance of prostate cancer (PCa). This review provides a comprehensive overview of the p53 pathway’s structure and function, with emphasis on the distribution characteristics and clinical implications of TP53 mutations in PCa. We systematically examine how these mutations correlate with disease aggressiveness, therapeutic resistance, and patient prognosis. In particular, the article delves into the mechanisms by which inactivation of the p53 pathway drives immune evasion, metabolic reprogramming, and alterations in the tumor microenvironment. We also highlight the synergistic interactions between p53 alterations and other key molecular events, including TMPRSS2-ERG fusion and PTEN loss, which together form a PCa-specific regulatory network that accelerates carcinogenesis and promotes lineage plasticity. Furthermore, the review discusses the emerging role of mutant p53 in shaping the immunosuppressive microenvironment and metabolic adaptations that underlie resistance to androgen deprivation therapy, radiotherapy, and chemotherapy. Finally, we address potential strategies and research challenges in targeting the p53 pathway for PCa treatment, including the development of small molecule reactivators, synthetic lethal approaches, and biomarker-directed combination therapies. This review offers a theoretical foundation and guidance for future basic research and clinical applications aimed at improving outcomes for patients with PCa.

Source: Translational Andrology and Urology

DOI: 10.21037/tau-2026-0645