Title:Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment
Volume: 18
Issue: 2
Author(s): Voon Yee-Lin*, Wong Pooi-Fong and Alan Khoo Soo-Beng
Affiliation:
- Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur,Malaysia
Keywords:
Apoptosis, Epstein-Barr virus (EBV), carcinoma, cisplatin, small molecule inhibitor, targeted molecular therapy.
Abstract: Nasopharyngeal carcinoma (NPC) is a form of head and neck cancer of multifactorial etiologies
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
chemotherapy, 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 chemotherapy. 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 administration 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 specifically 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 producing 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.
