Yoshizaki Tomokazu, Ito Makoto, Murono Shigekyuki, Wakisaka Naohiro, Kondo Satoru, Endo Kazuhira
Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, Japan.
Auris Nasus Larynx. 2012 Apr;39(2):137-44. doi: 10.1016/j.anl.2011.02.012. Epub 2011 May 17.
Nasopharyngeal carcinoma (NPC) is a kind of rare head and neck cancer in Japan. However, NPC has some unique features. It is one of the most popular cancers in southern China, Southeast Asia, the Arctic, and the middle East/north Africa. This distinctive racial, ethnical, and geographic predisposition to NPC implies that both genetic susceptibility and environmental factors contribute to the development of this tumor. NPC is an Epstein-Barr virus - associated tumor. Consistent elevation of EBV antibody titers is a well-established risk factor of development of NPC. Not only pathophysiological relationship, but also molecular mechanism of EBV-mediated carcinogenesis has been enthusiastically investigated. LMP1, an EBV primary oncogene, upregulates each step of metastasis, and contribute to highly metastatic feature of NPC. A tumor suppressor gene p53 is mostly intact and overexpressed in NPC whereas expression of p16, a cyclin-dependent kinase inhibitory protein, is downregulated in 2/3 of NPC. Intention modulated radiotherapy (IMRT) is now getting prevalent for the treatment of NPC because of complicated structure and location of nasopharynx. A good therapeutic result can be achieved by distributing a high dose to the tumor while keeping down normal tissue complications by reducing radiation dose to normal tissues. Chemotherapy is important to control distant metastasis of chemoradiosensitive NPC, and thus, should play an important role. However, most effective combination of anti-tumor drugs, protocol of chemoradiotherapy has not well-established. Finally, molecular targeting therapy, including targeting EBV gene product, has been developing and on the way to the clinical use.
鼻咽癌(NPC)在日本是一种罕见的头颈癌。然而,NPC有一些独特的特征。它是中国南方、东南亚、北极地区以及中东/北非地区最常见的癌症之一。这种NPC独特的种族、民族和地理易感性表明,遗传易感性和环境因素都对这种肿瘤的发生发展有影响。NPC是一种与爱泼斯坦-巴尔病毒(EBV)相关的肿瘤。EBV抗体滴度持续升高是公认的NPC发生的危险因素。不仅EBV介导的致癌作用的病理生理关系,而且其分子机制都得到了积极的研究。LMP1是一种EBV原癌基因,它上调转移的各个步骤,并促成NPC的高转移特性。肿瘤抑制基因p53在NPC中大多保持完整并过度表达,而细胞周期蛋白依赖性激酶抑制蛋白p16的表达在2/3的NPC中下调。由于鼻咽部结构和位置复杂,调强放射治疗(IMRT)目前在NPC治疗中越来越普遍。通过向肿瘤部位给予高剂量辐射,同时通过降低对正常组织的辐射剂量来减少正常组织并发症,可以取得良好的治疗效果。化疗对于控制放化疗敏感的NPC的远处转移很重要,因此应发挥重要作用。然而,最有效的抗肿瘤药物组合、放化疗方案尚未完全确立。最后,包括靶向EBV基因产物在内的分子靶向治疗一直在发展,并正朝着临床应用迈进。