Abstract

The Epstein–Barr virus (EBV) is the first cancer virus which infects more than 90 % of human population although most individuals are healthy carriers. It can cause a variety of diseases but I focus on nasopharyngeal carcinoma (NPC), and which is 100 % associated with EBV. NPC is a common cancer in the southern China region, including Hong Kong. As can be seen, EBV is one of the most important risk factors for NPC. EBV contributes to the clonal expansion of the EBV-infected epithelial cell, which is able to survive with accumulation of more oncogenic mutations. With those mutations accumulated in the presence of EBV, the mutated cells eventually develop into aggressive cancer cells and contribute to tumor growth and progression. Thus, there is a strong bond between EBV infection and NPC development. NPC patients with advanced diseases/recurrent cases/after standard therapies can suffer from cancer cachexia with high frequencies. Cancer cachexia is a wasting symptom and defined as body weight loss more than 5 percent over 12 months or less. This symptom decreases the quality of life and reduces the survival rate of NPC patients, since it decreases patients’ response towards radio-, chemo-, and immune-therapy. In cancer cachexia, excessive secretion of proinflammatory cytokines IL6 and TNF-alpha by tumor cells can cause adipose and muscle tissue wasting. “White fat browning” has been recently shown to be closely associated with the loss of white adipose. Effective treatments for cancer cachexia are not yet available. The elimination of EBV is a tough challenge as most of the time the virus remains in a latent status, which produces very few gene products that can serve as therapeutic targets. The consistent expression of the EBV latent protein, EBV nuclear antigen 1 (EBNA1) and the well-known EBV oncoprotein, latent membrane protein 1 (LMP1), represent the few EBV target proteins. Numbers of EBV-targeting peptides (EBNA1-, LMP1-, and dual-targeting) have been developed in our laboratory. As EBV latent infection could contribute to the proinflammatory cytokine production, this project aims to test if any of those anti-EBV drugs can be used to treat NPC cachexia, using a number of in vivo animal models. 

Reference:

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