文章：

头颈癌的分子生物学

The molecular biology of head and neck cancer

原文发布日期：2010-12-16

DOI: 10.1038/nrc2982

类型: Review Article

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要点：

1. Head and neck squamous cell carcinomas (HNSCCs) develop in the mucosal linings of the upper aerodigestive tract and are the sixth leading cause of cancer worldwide. Risk factors are exposure to carcinogens, most notably tobacco smoking and alcohol consumption, infection with high-risk types of human papillomavirus (HPV) and genetic predisposition.
2. HNSCC is a heterogeneous disease. At least two genetic subclasses can be distinguished: HPV-positive and HPV-negative tumours. Preliminary data suggest that further subclassification is likely to follow.
3. A key issue in HNSCC pathogenesis is that carcinomas develop within large preneoplastic fields of mucosal epithelium made up of genetically altered cells that are clonally related to the carcinoma and often extend into the surgical margins when tumours are excised, and can cause local recurrences and second primary tumours.
4. Limitless replicative potential of head and neck cancer cells is caused by abrogation of the p53 and retinoblastoma (RB) pathways that perturb cell cycle regulation, probably in the context of telomerase reverse transcriptase (TERT) expression.
5. A subgroup of HNSCCs becomes independent from growth factors owing to somatic changes in the epidermal growth factor receptor (EGFR) signalling pathway.
6. Some, if not all, HNSCCs escape from the growth inhibitory transforming growth factor-β (TGFβ) pathway by somatic mutation or chromosome loss of key genes. This pathway seems to be interconnected to the nuclear factor-κB (NF-κB) pathway.
7. Somatic mutations and genetic changes indicate that the PI3K–PTEN–AKT pathway is frequently activated in HNSCC.
8. Metastatic dissemination of HNSCC is initially to the lymph nodes in the neck. Expression profiles predict lymph node metastasis, but causative cancer genes have not yet been identified.
9. The unravelling of the biological characteristics of HNSCC will lead to novel and personalized therapies in the near future.

要点翻译：

1. 头颈部鳞状细胞癌（HNSCC）发生于上呼吸消化道的黏膜内衬，是全球第六大常见癌症。其危险因素包括接触致癌物（最显著的是吸烟和饮酒）、高危型人乳头瘤病毒（HPV）感染以及遗传易感性。
2. HNSCC是一种异质性疾病，至少可区分为两种遗传亚型：HPV阳性肿瘤和HPV阴性肿瘤。初步数据表明后续很可能出现更精细的亚型分类。
3. HNSCC发病机制的关键在于：癌变发生于巨大的黏膜上皮瘤前病变区域内，这些区域由与癌细胞存在克隆关系的遗传变异细胞构成。手术切除肿瘤时，这些病变常延伸至手术切缘，可能导致局部复发和第二原发肿瘤。
4. 头颈癌细胞通过破坏p53和视网膜母细胞瘤（RB）通路获得无限复制潜能，该过程可能伴随端粒酶逆转录酶（TERT）的表达。
5. 部分HNSCC因表皮生长因子受体（EGFR）信号通路的体细胞变异而实现生长因子非依赖性增殖。
6. 多数HNSCC通过关键基因的体细胞突变或染色体缺失，逃逸生长抑制性TGF-β通路调控，该通路似乎与核因子κB（NF-κB）通路存在交互作用。
7. 体细胞突变和遗传改变表明PI3K-PTEN-AKT通路在HNSCC中频繁激活。
8. HNSCC的转移首先累及颈部淋巴结。虽然基因表达谱可预测淋巴结转移，但尚未明确其致病癌基因。
9. 对HNSCC生物学特征的深入解析将在不久的将来推动个体化新疗法的诞生。

英文摘要：

Head and neck squamous cell carcinomas (HNSCCs) are caused by tobacco and alcohol consumption and by infection with high-risk types of human papillomavirus (HPV). Tumours often develop within preneoplastic fields of genetically altered cells. The persistence of these fields after treatment presents a major challenge, because it might lead to local recurrences and second primary tumours that are responsible for a large proportion of deaths. Aberrant signalling pathways have been identified in HNSCCs and inhibition of epidermal growth factor receptor (EGFR) has proved a successful therapeutic strategy. In this Review, we discuss the recent literature on tumour heterogeneity, field cancerization, molecular pathogenesis and the underlying causative cancer genes that can be exploited for novel and personalized treatments of patients with HNSCC.

摘要翻译： 

头颈部鳞状细胞癌（HNSCCs）由烟草和酒精摄入以及高危型人乳头瘤病毒（HPV）感染引起。肿瘤常在基因改变的癌前病变区域内发生。治疗后这些区域的持续存在是主要挑战，因其可能导致局部复发和第二原发肿瘤，这是导致大量死亡的原因。HNSCCs中已发现异常信号通路，抑制表皮生长因子受体（EGFR）已被证实为有效的治疗策略。在本综述中，我们讨论肿瘤异质性、区域癌变、分子发病机制及可 exploited 的致癌基因，以实现HNSCC患者的新型个体化治疗。

原文链接：

The molecular biology of head and neck cancer