| dc.description.abstract | The latent form of Epstein-Barr virus (EBV) is associated with many
malignancies, including nasopharyngeal carcinoma, which makes EBV itself an
attractive target of therapy. The reactivation of EBV toward lytic gene
expression cascade will lead to expression of proteins involved in viral genome
replication and formation of new virions, which will induce a strong immune
response. The kinases expressed exclusively during the lytic cycle will also
sensitize the tumor cells to antiviral treatment. This concept has recently been
incorporated into a combination therapy, referred to as cytolytic virus activation
therapy, in which a combination of gemcitabine (a chemoagent), valproic acid (a
histone deacetylase inhibitor) and subsequent addition of ganciclovir (an
antiviral agent), has been used in clinical studies with promising results. The
molecular mechanisms by which these compounds co-operate, in order to
trigger DNA damage response with subsequent lytic induction and tumor
cytotoxicity, is discussed in this review. These agents are shown to work in
multiple ways together. However, other EBV-associated malignancies might
benefit form different set of compounds and this needs to be investigated.
Further studies are required to analyze the effect of different combinations, in
order to create potential stronger responses. These informations will be highly
beneficial to treat other EBV-associated malignancies by use of EBV as the
main target in a combination therapy. | |
