The molecular pathogenesis of head and neck squamous cell carcinoma
The molecular pathogenesis of head and neck squamous cell carcinoma
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DOI：
10.1172/jci59889
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发表时间：
2012-06-01
影响因子：
15.9
通讯作者：
Ellisen, Leif W.
中科院分区：
文献类型：
--
作者：
Rothenberg, S. Michael;Ellisen, Leif W.
头颈部鳞状细胞癌（HNSCC）是一种相对常见的人类癌症，其特点是高发病率、高死亡率，除了手术、标准的细胞毒性化疗和放疗外，几乎没有治疗选择。虽然最重要的风险因素是吸烟和饮酒，但该疾病也与感染高危型人乳头瘤病毒（hpv）有关。最近的遗传分析对该病的分子发病机制有了新的认识。总体而言，尽管包括PIK3CA和RAS在内的经典癌基因中的体细胞激活突变发生在HNSCC中，但它们相对不常见。相反，遗传数据指出多种肿瘤抑制通路，包括p53、Rb/INK4/ARF和Notch，在肿瘤的发生、发展和维持中起作用。HNSCC遗传学知识的日益完善，再加上越来越复杂的动物模型和更新的药物靶向策略，应该会促进新的治疗方法和改善疾病的结果。
Squamous cell carcinoma of the head and neck (HNSCC) is a relatively common human cancer characterized by high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Although the most important risk factors are tobacco use and alcohol consumption, the disease is also linked to infection with high-risk types of human papilloma viruses (HPVs). Recent genetic analyses have yielded new insights into the molecular pathogenesis of this disease. Overall, while somatic activating mutations within classical oncogenes including PIK3CA and RAS occur in HNSCC, they are relatively uncommon. Instead genetic data point to a contribution of multiple tumor suppressor pathways, including p53, Rb/INK4/ARF, and Notch, in tumor initiation, progression, and maintenance. The increasingly refined knowledge of HNSCC genetics, combined with ever-more-sophisticated animal models and newer drug targeting strategies, should promote novel therapeutic approaches and improved disease outcomes.