Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment

摘要

Nasopharyngeal carcinoma (NPC) is a form of head and neck cancer of multifactorial etiologiesthat is highly prevalent among men in the population of Southern China and Southeast Asia.NPC has claimed many thousands of lives worldwide; but the low awareness of NPC remains a hindrancein early diagnosis and prevention of the disease. NPC is highly responsive to radiotherapy andchemotherapy, but radiocurable NPC is still dependent on concurrent treatment of megavoltage radiotherapywith chemotherapy. Despite a significant reduction in loco-regional and distant metastases, radiotherapyalone has failed to provide a significant improvement in the overall survival rate of NPC,compared to chemotherapy. In addition, chemo-resistance persists as the major challenge in the managementof metastatic NPC although the survival rate of advanced metastatic NPC has significantlyimproved with the administration of chemotherapy adjunctive to radiotherapy. In this regard, targetedmolecular therapy could be explored for the discovery of alternative NPC therapies. Nutlin-3, a smallmolecule inhibitor that specifically targets p53-Mdm2 interaction offers new therapeutic opportunitiesby enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumorsuppression pathway while producing minimal cytotoxicity and side effects. This review discussesthe potential use of Nutlin-3 as a p53-activating drug and the future directions of its clinical researchfor NPC treatment.