**10. Conclusion**

NPC is a very interesting within the other head and neck cancers, occurring in young patients non-smokers/non drinkers and significant improvement of therapeutic results have been reached during the last 30 years, 5 years-OS increasing from 20-30% to more than 75% with the recent protocols of CT-RT or PCT followed by CT-RT that included taxanes (Boussen et al, 2010, Chan et al,2010). Overexpression of EGRF, present in more than 70% of NPC leads to the use of Cetuximab as adjuvant concomitant or maintenance therapy (Yang Y et al, 2011). Anti-angiogenesis therapies like Pazopanib have been also tested without proven efficacy(Lim et al,2011). The significant survival improvement made NPC a more curable disease and efforts were made to reduce late sequelae specially in children and adolescents and to affect minimally quality of life after combined chemo-radiotherapy (Fang et al,2011;Marucci et al,2011;Shueng et al,2011).

## **11. References**

Al-Sarraf M, LeBlanc M, Giri PG et al. (1998).Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. *J Clin Oncol*,16,1310–1317.

found to be a significant prognostic factor on LRRFS (p=0.03). However Nasopharyngeal PTV alone is missing the volume of satellite cervical nodes that have probably an important

NPC failures are mainly metastatic, to bones, lungs and liver and loco-regional relapses became more rare due to the high loco-regional control rate obtained by loco-regional RT (Leung et al,2005; Cvitkovic et al,1993). In metastatic situations, NPC remains chemosensitive to cisplatin, adriamycin, 5Fluorouracil or more recently taxanes, gemcitabine or oral capecitabine(Boussen et al,1991,2010;You et al,2011;Bensouda et al,2011). Prolonged survival after palliative CT and/or RT could be observed in patients with bone metastases in case of bone MTS only and less than 4 sites involved (Fandi et al,2000;Cao et al,2011). In isolated bone metastases, prolonged responses under biphosphonates plus CT have been also reported, with a significant reduction of skeletal events and better (11.5 vs 5.5 months, P < 0.001) progression-free survival and overall survival (23.5 vs. 17.5 months, P < 0.001) of combined vs chemotherapy alone group. (Jin et al,2011). Even in case of lung MTS disease, different prognostic groups could be identified according to size and numbers of metastatic

Some efforts have been done oriented for early detection in relatives of patients considered at high risk for NPC, according to their viral DNA and anti-EBV profile (Baizig et al,2011;Liu et al,2011). Sophisticated endoscopic technique have been also tested to detect easily early

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Al-Sarraf M, LeBlanc M, Giri PG et al. (1998).Chemoradiotherapy versus radiotherapy in

patients with advanced nasopharyngeal cancer: phase III randomized Intergroup

prognostic value.

**8. Recurrent/metastatic disease** 

nodules (Cao X et al, 2011).

**10. Conclusion** 

**11. References** 

**9. Effective screening for NPC?** 

stages of NPC (Lin et al,2011, Lin et al,2011).

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**11** 

*Taiwan* 

Shih-Shun Chen

 **Potential Therapeutic Molecular Targets** 

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.

Virus binding to the surface of a target cell is a major determinant of cellular tropism and is a critical step in viral pathogenesis. This early event initiates the virus replication cycle by the attachment of the virus to specific receptor (s) and leads to the release of the viral genome into the cytoplasm of the target cell. It is believed that EBV infection is initiated by

**2. The molecular mechanisms of EBV infection and the effects on** 

**NPC growth and metastasis** 

**1. Introduction** 

**for Nasopharyngeal Carcinoma** 

*Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung,* 

