Identification of Epstein–Barr Virus as a Target in Nasopharyngeal Carcinoma Treatment

Nasopharyngeal carcinoma (NPC) is a malignancy that originates from the epithelial cells extending over the nasopharyngeal surface. This disease is more popular in Southeast Asian countries, Northern Africa, and the Middle East and closed related to Epstein-Barr virus (EBV) infection. EBV had been identified as a potential therapeutic target in some EBV related cancer such as lymphoma and NPC. In cancer cell, EBV was in latent phase and expressed 8-11 genes for maintaining EBV proliferation. After switching to lytic phase, almost all the EBV encoding genes were expressed including thymidine kinase (TK) and some highly immunogenetic genes. These latent-lytic phase switcher included DNA methyltransferase inhibitors (nucleoside analogues such as 5-aza-2'-deoxycytidine/decitabine/DAC, 5-azacytidine, and zebularine), various histone deacetylase (HDAC) inhibitors, radiotherapy and chemotherapy. Although in some lymphoma subtype, HDAC inhibitor combined with antivirus drug can cause tumor lytic syndrome. Recently, combined chemotherapy and viral lytic therapy, cytolytic viral activation therapy (CVAT) had been shown some promising result in pilot study of NPC. Our group had established patient derived xenograft (PDX) animal model which harboring EBV from NPC metastatic sites. We will use this model to test the drug sensitivity and CVAT. The following aims will be proposed: Aim 1: Testing the individual drug efficacy in EBV positive NPC cell line(s). 1-1 in vitro studies, drug sensitivity test via cell growth assay 1-2 in vivo cell line xenograft in SCID mice drug sensitivity studies Aim 2: Test the CVAT in EBV positive NPC tumor animal model in PDX system 2-1 Establish PDX system from different human metastatic site tumor 2-2 Characterization the PDX including microarray and EBV DNA load 2-3 Drug sensitivity screening and clinical correlation 2-4 Test CVAT in PDX system

Project ID:PC10408-2495
External Project ID:MOST104-2314-B182-036