Completed clinical trials of p53-targeted therapeutic strategies in cancer: A cross-sectional ClinicalTrials.gov registry analysis.

Abstract

The tumor suppressor gene TP53 is one of the most frequently altered genes in human cancers and plays a central role in regulating cell cycle arrest, apoptosis, and genomic stability. Therapeutic strategies targeting the p53 pathway have been investigated to restore or exploit p53 function in human malignancies. However, the characteristics, reporting completeness, and clinical development patterns of completed trials evaluating p53-targeted therapeutic strategies have not been comprehensively summarized. This study aims to characterize the design, therapeutic strategies, reporting completeness, and primary objectives of completed clinical trials investigating p53-targeted therapeutic strategies for cancer. A cross-sectional registry analysis of ClinicalTrials.gov was conducted using the search terms "Cancer" AND "p53 gene therapy." Completed studies available as of 1 July 2025 were screened for eligibility. Trials investigating p53-targeted therapeutic strategies, including p53 gene therapy and other therapeutic approaches directly targeting the p53 pathway, were included. Data extracted included study design, cancer type, therapeutic strategy, clinical phase, enrollment, and primary outcome measures. Descriptive statistics were used to summarize study characteristics; no inferential statistical analyses were performed. Twenty-three completed studies met the eligibility criteria, including 20 (87.0%) interventional and 3 (13.0%) observational studies. The included studies evaluated diverse p53-targeted therapeutic strategies, including adenoviral vector-mediated p53 gene therapy, chemotherapy combinations, immunotherapeutic approaches, biomarker-guided treatment strategies, and molecularly targeted therapies. Early-phase clinical development predominated, with Phase I studies accounting for the largest proportion of completed trials. Enrollment information was available for 17 (73.9%) studies, whereas six (26.1%) did not report participant numbers. Primary outcome measures were reported for 15 (65.2%) studies, while eight (34.8%) lacked clearly defined primary outcomes. Five studies (21.7%) had publicly posted study results on ClinicalTrials.gov, whereas 18 (78.3%) had no posted results available. Reported primary endpoints predominantly focused on safety, dose escalation, treatment feasibility, and biomarker evaluation. Completed clinical trials investigating p53-targeted therapeutic strategies remain predominantly in the early stages of clinical development and have primarily focused on evaluating safety, feasibility, and preliminary biological activity rather than definitive treatment efficacy. Variability in registry reporting, including incomplete enrollment, primary outcome, and study result reporting, limits comprehensive assessment of the current evidence base.