Potential Therapeutic Molecular Targets for Nasopharyngeal Carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is the leading cause of death in Southeast Asian populations, especially among Chinese people (338). The specific type of NPC is defined by the World Health Organization and classified histologically as either type I (keratinizing squamous cell carcinoma), type II (non-keratinizing squamous cell carcinoma), or type III (undifferentiated carcinoma) (263). Etiologic factors associated with NPC development are classified according to three determinants, including genetic susceptibility, Epstein-Barr virus (EBV) infection, and environmental exposure to carcinogens (45, 337). Evidence has indicated that EBV infection is implicated in the development of type II and III and is observed particularly in Asia (50, 61, 205, 230). EBV infection is generally not detected in type I NPC patients, especially in non-endemic areas (221, 342). Potential risk factors significantly associated with the initiation and development of type I NPC are cigarette smoking and alcohol consumption (35, 225, 295, 301). However, increasing evidence indicates that EBV appears to be the predominant risk factor associated with the initiation and development of NPC, regardless of histological type (17, 20, 300). In particular, EBV infection is an important event in the early stage of the NPC carcinogenesis process before tumor formation (101). Clinically, NPC exhibits a high incidence of lymph node spread and distant metastasis that is correlated with a poor prognosis, even when employing radiation therapy and chemotherapy (43, 260, 326). In the search for new substances with anti-tumoral effects, many natural compounds from dietary plants, such as herb and fruit extracts, have been shown to inhibit NPC proliferation, invasion, metastasis, and angiogenesis both in vitro and in vivo. This review summarizes the molecular mechanisms of EBV infection in NPC development as well as the role of natural compounds in the regulation of multiple cellular pathways and their clinical importance for the prevention and treatment of NPC.