Prognostic Value of Molecular Markers and Implication for Molecular Targeted Therapies in Nasopharyngeal Carcinoma: An Update in an Era of New Targeted Molecules Development

Abstract

The aim of the study was to evaluate the prognostic significance of molecular biomarkers which could provide information for more accurate prognostication and development of novel therapeutic strategies for nasopharyngeal carcinoma (NPC). NPC is a unique malignant epithelial carcinoma of head and neck region, with an intimate association with the Epstein-Barr virus (EBV). Currently, the prediction of NPC prognosis is mainly based on the clinical TNM staging; however, NPC patients with the same clinical stage often present different clinical outcomes, suggesting that the TNM stage is insufficient to precisely predict the prognosis of this disease. In this review, we give an overview of the prognostic value of molecular markers in NPC and discuss potential strategies of targeted therapies for treatment of NPC. Molecular biomarkers, which play roles in abnormal proliferation signaling pathways (such as Wnt/β-catenin pathway), intracellular mitogenic signal aberration (such as hypoxia-inducible factor (HIF)-1α), receptor-mediated aberrations (such as vascular endothelial growth factor (VEGF)), tumor suppressors (such as p16 and p27 activity), cell cycle aberrations (such as cyclin D1 and cyclin E), cell adhesion aberrations (such as E-cadherin), apoptosis dysregualtion (such as survivin) and centromere aberration (centromere protein H), are prognostic markers for NPC. Plasma EBV DNA concentrations and EBV-encoded latent membrane proteins are also prognostic markers for NPC. Implication of molecular targeted therapies in NPC was discussed. Such therapies could have potential in combination with different cytotoxic agents to combat and eradicate tumor cells. In order to further improve overall survival for patients with loco-regionally advanced NPC, the development of innovative strategies, including prognostic molecular markers and molecular targeted agents is needed.

RETRACTED ARTICLE: MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2

“…Though enhanced susceptibility to radiotherapy and excellent local control can be achieved with advances in radiotherapy and chemotherapy, the effectiveness of these treatments requires further improvements, especially with distant metastasis rates and high local recurrence rates [4]. In fact, 30% ~ 40% of NPC patients will develop distant metastasis within 4 years, and the prognoses become poor upon metastasis [5]. Metastasis, related to poor prognosis and death of cancer, is primarily responsible for the recurrence and initiating metastatic behaviours [6].…”

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy

“…The differences were all statistically significant, with the exception of distant metastasis. In multivariate analysis, EGFR extent was the only independent factor that predicted disease relapse, loco-regional failure, and mortality due to cancer (48). The present study hypothesized that treatment insensitivity was the primary reason for this unsatisfied curative effect.…”

Pinostilbene Hydrate Inhibits the Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Downregulating MMP-2 Expression and Suppressing Epithelial–Mesenchymal Transition Through the Mitogen-Activated Protein Kinase Signaling Pathways

“…Liu et al demonstrated an increased MMP-9 level as an unfavorable prognostic factor for NPC; patients with elevated MMP-9 level had a significantly shorter overall survival (OS) time and higher MMP-9 level was positively associated with the status of lymph node metastasis and clinical stage (39). Therefore, MMPs inhibitor had become one of molecular targeted therapy in development for treatment of NPC (40). One study had shown zoledronic acid (MMP inhibitor) combined with chemotherapy could improve progression-free survival (PFS) and OS in NPC patients with bone metastases (41).…”

“…EMT is also recognized as an important step in the metastasis of malignancies and the level of E-cadherin was negatively correlated with the clinical prognosis in NPC (40, 43–45). Nowadays demethylation of E-cadherin gene is considered to be a potential therapeutic strategy for patients with NPC (46).…”