Treatment of Nasopharyngeal Carcinoma: Therapeutic Management and Future View of Epstein-Barr Virus-Targeting Treatment

Shigeyuki      Murono; Satoru      Kondo; Naohiro      Wakisaka; Tomokazu      Yoshizaki

doi:10.2174/157339409788982269

Abstract

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic tumor, which is universally associated with Epstein-Barr virus (EBV). Clinically, radiotherapy, but not surgery, is usually performed for the treatment of NPC because of the deep and complex location of the tumor. Previous randomized trials did not demonstrate that either neoadjuvant or adjuvant chemotherapy offered survival advantages over radiotherapy alone. Therefore, concurrent chemoradiotherapy consisting of three courses of CDDP administration during radiotherapy followed by three courses of adjuvant chemotherapy with 5-FU and CDDP is the widely accepted treatment modality at present. Further efforts have been attempted to establish less intensive but more or equally effective treatment, including an alternating chemoradiotherapy consisting of three courses of chemotherapy with 5-FU and CDDP accompanied by radiotherapy during their intervals. Furthermore, the association of NPC with EBV can be applied to treatment with antiviral drugs. The phosphonated nucleoside analog, cidofovir, inhibits and prevents NPC xenografts in nude mice. However, the highly metastatic capability of NPC has been linked to the EBV oncoprotein, latent membrane protein 1 (LMP1). LMP1 promotes metastasis through induction of matrix metalloproteinase-9, vascular endothelial growth factor, fibroblast growth factor-2, MUC1 as well as an epithelial-mesenchymal transition through various signaling pathways such as nuclear factor kappa-B and others. The article will review currently developing clinical treatment methods as well as therapeutic possibilities from the perspective of an EBV-associated treatment of NPC.

Keywords: Nasopharyngeal carcinoma, Concurrent chemoradiotherapy, Epstein-Barr virus, Cidofovir, LMP1

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