Completed Clinical Trials of p53 Gene Therapy in Cancer: A ClinicalTrials.gov-Based Analysis

Background The tumour suppressor gene TP53, frequently mutated in various different types of cancers, plays a vital role in regulating cell cycle arrest, apoptosis, and genomic stability. Gene therapy targeting p53 aims to restore its normal function in tumours with defective p53, offering a novel therapeutic approach. Objective This study aims to systematically characterise the design, therapeutic strategies, and primary outcomes of completed clinical trials investigating p53 gene therapy for cancer, focusing on study design, targeted conditions, intervention strategies, and clinical outcomes. Methods A systematic search of ClinicalTrials.gov database was conducted using the keywords “Cancer” AND “p53 gene therapy,” filtered for completed studies. A total of 23 eligible trials were included. Data on cancer type, intervention, study phase, enrolment, and primary outcomes were extracted and analysed descriptively. Results Of the 23 included trials, 20 (87%) were interventional and 3 were observational. Gene therapy interventions were used in 5 trials, while chemotherapy was included in 13. The most studied conditions were bladder, breast, ovarian, and lung cancers. Adenoviral vectors such as Ad5CMV-p53 were the predominant gene therapy platform. Many trials combined p53 gene therapy with chemotherapy, surgery, or radiation. Total reported enrolment across studies was 2,846 participants. Most trials focused on safety, dose escalation, and biomarker analysis rather than definitive clinical efficacy. Conclusion Completed clinical trials on p53 gene therapy in cancer suggest promising biological rationale but limited clinical translation to date. Most studies remain early-phase, with sparse progression to large-scale efficacy trials. Future efforts should prioritize stratified patient populations, refined gene delivery technologies, and combination approaches to enhance therapeutic impact.