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

Nasopharyngeal carcinoma (NPC) is a form of head and neck cancer of multifactorial etiolo-gies that 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 hindrance in early diagnosis and prevention of the disease. NPC is highly responsive to radiotherapy and chemothera-py, but radiocurable NPC is still dependent on concurrent treatment of megavoltage radiotherapy with chemotherapy. Despite a significant reduction in loco-regional and distant metastases, radiotherapy alone has failed to provide a significant improvement in the overall survival rate of NPC, compared to chemo-therapy. In addition, chemo-resistance persists as the major challenge in the management of metastatic NPC although the survival rate of advanced metastatic NPC has significantly improved with the admin-istration of chemotherapy adjunctive to radiotherapy. In this regard, targeted molecular therapy could be explored for the discovery of alternative NPC therapies. Nutlin-3, a small molecule inhibitor that specifi-cally targets p53-Mdm2 interaction offers new therapeutic opportunities by enhancing cancer cell growth arrest and apoptosis through the restoration of the p53-mediated tumor suppression pathway while pro-ducing minimal cytotoxicity and side effects. This review discusses the potential use of Nutlin-3 as a p53-activating drug and the future directions of its clinical research for NPC treatment.