Current Status and Challenges of Targeting the p53-MDM2 Axis
ZHENG Keke1, FU Caiyun1, JIN Juan1, WANG Xi1,2*
Malignant tumors constitute a grave threat to human health. Although significant progress has been made in tumor pharmacotherapy in recent years, challenges including low response rates, dose-limiting toxicities, and drug resistance persist. What’s worse, the five-year survival rate for patients with advanced tumors remains unsatisfactory. Therefore, it’s necessary and urgent to develop novel, highly effective and safe targeted therapeutics. The p53-MDM2 axis plays a critical role in the regulation of tumorigenesis and progression. Targeting this axis to reinstate the tumor-suppressive function of p53 has emerged as a prominent direction in the field of cancer targeted therapy. This review systematically delineates the molecular mechanisms of the p53-MDM2 axis, summarizes the research advances in drugs targeting this pathway for cancer treatment, and critically analyzes the challenges en- countered during clinical translation, aiming to offer insights for innovative strategies in cancer targeted therapy.
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