Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein–Barr Virus Infection

Abstract

Epstein–Barr virus (EBV), a type 4 γ herpes virus, is recognized as a causative agent in nasopharyngeal carcinoma (NPC). Incidence of EBV-positive NPC have grown in recent decades along with worse outcomes compared with their EBV-negative counterparts. Latent membrane protein 1 (LMP1), encoded by EBV, induces NPC progression. The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptor tyrosine kinases (RTK), is a driver of tumorigenesis, including for NPC. Little data exist on the relationship between EGFR and EBV-induced NPC. In our initial review, we found that LMP1 promoted the expression of EGFR in NPC in two main ways: the NF-κB pathway and STAT3 activation. On the other hand, EGFR also enhances EBV infection in NPC cells. Moreover, activation of EGFR signalling affects NPC cell proliferation, cell cycle progression, angiogenesis, invasion, and metastasis. Since EGFR promotes tumorigenesis and progression by downstream signalling pathways, causing poor outcomes in NPC patients, EGFR-targeted drugs could be considered a newly developed anti-tumor drug. Here, we summarize the major studies on EBV, EGFR, and LMP1-regulatory EGFR expression and nucleus location in NPC and discuss the clinical efficacy of EGFR-targeted agents in locally advanced NPC (LA NPC) and recurrent or metastatic NPC (R/M NPC) patients.

EBV‑positive large‑cell and small‑cell neuroendocrine carcinoma of the nasopharynx: A case report and review of the literature

“…EBV infection is common worldwide and is associated with infectious mononucleosis, Burkitt's lymphoma, classical Hodgkin's lymphoma, gastric cancers and NPC ( 26 ). Almost 98% of NPC cases are closely related to EBV infection ( 27 ), which may promote the progression of NPC ( 28 ). A large number of studies have indicated that the level of free EBV DNA in the plasma of patients with NPC is highly correlated with its prognosis and is widely used as a clinical marker in the clinical diagnosis and monitoring of NPC ( 1 , 29 ).…”

“…In contrast to the present findings, it has been reported that EGFR overexpression is a potential prognostic biomarker for advanced-stage patients with a poor outcome and is relatively common in NPC ( 32 ). Furthermore, EGFR is highly expressed in EBV-infected cells and may promote the neoplastic transformation of EBV-positive cells; importantly, EGFR may be necessary for the internalization and fusion of EBV in NPC cells ( 28 ). However, only a small amount of information regarding EGFR expression is available ( 5 – 22 ), despite non-small cell cancers, including large-cell cancers, being associated with EBV infection ( 6 , 10 , 13 , 15 , 19 ).…”

Updates on Epstein–Barr Virus (EBV)-Associated Nasopharyngeal Carcinoma: Emphasis on the Latent Gene Products of EBV

“…The virus mimics latency models seen in certain malignant tumors linked to EBV and utilizes them for various viral life cycle stages [ 11 ]. EBV must also multiply periodically during its life cycle to generate infectious virus for transmission to a new sensitive host, with epithelial regions in the oropharynx and salivary glands showing the main viral replication sites [ 108 ]. Thus, the natural history of chronic EBV infection is comparable to that of another herpesviruses.…”

“…Despite the fact that around half of individuals living in China or moving to Southeast Asia have NPCs, the recurrence is significantly higher among Chinese born in Western nations than Caucasians [ 77 ]. Likewise, contrasted with French men born in the south of France, French men born in North Africa had a higher risk of NPC [ 108 ].…”

Exploration of the effect of Celastrol on protein targets in nasopharyngeal carcinoma: Network pharmacology, molecular docking and experimental evaluations

“…The onset is concealed, and the main pathological types of most cancers are medium and low-differentiated squamous cell carcinoma. Clinically, radiotherapy combined with chemotherapy has achieved favorable results in early-stage patients, but a considerable number of patients still experience metastasis and recurrence, thus affecting their prognosis ( Peng et al, 2021 ). Therefore, other prevention and treatment strategies need to be developed in the clinic.…”