Title:Histone Modifications as Molecular Targets in Nasopharyngeal Cancer
Volume: 23
Issue: 2
Author(s): Sukanya Shyamasundar, S. Thameem Dheen and B. Huat Bay
Affiliation:
Keywords:
Epigenetics, DNA methylation, histone deacetylase inhibitor, histone modifications, microRNA, molecular
therapy, nasopharyngeal carcinoma.
Abstract: Nasopharyngeal carcinoma (NPC) is a cancer of the nasopharyngeal
epithelium with distinct geographical, ethnic and racial distribution. Several
genetic, ethnic and environmental risk factors, have been implicated in nasopharyngeal
pathogenesis and of significance, is the Epstein - Barr virus (EBV)-
latent infection observed in most patients. Patients with NPC are typically diagnosed
only in advanced stages due to non-specific symptoms, and hence,
they respond poorly to therapy. Currently, low survival rates, severe complications, tumour metastasis and recurrence
following chemo-radiotherapy, delineate the need for better therapeutic options to combat the disease.
Recent studies have shown that epigenetic mechanisms such as DNA methylation, histone modifications
and microRNAs, which are altered in the EBV genome as well as in the host cells, may underlie the initiation
and progression of NPC. Histone acetylation and deacetylation which are mediated by enzymes, namely histone
acetyl transferases (HATs) and histone deacetylases (HDACs), are known to regulate gene expression
and several cellular processes. HDACs are also involved in maintaining the EBV latent cycle and thus,
HDAC inhibitors (HDACi) are potent inducers of EBV reactivation, which is critical for the expression of the
lytic proteins, thereby providing novel targets for therapy, as well as mediating enhanced killing of cancer
cells, when used alone or along with additional anti-cancer agents in EBV associated malignancies. Recently,
three FDA- approved HDACi have been used for the treatment of T-cell lymphoma, while several others are
in clinical trials, making histone modifications excellent candidates for targeted therapy. In this review, we
summarize the epigenetic mechanisms altered in NPC, with a focus on histone modifications for targeted
therapy.
