文章：

非小细胞肺癌：一组异质性疾病

Non-small-cell lung cancers: a heterogeneous set of diseases

原文发布日期：2014-07-24

DOI: 10.1038/nrc3775

类型: Review Article

开放获取: 否

要点：

1. Next-generation sequencing and other high-throughput analyses have begun to show the many different molecular and genetic subsets of non-small-cell lung cancer (NSCLC) and have drastically altered the clinical evaluation and treatment of patients during the past decade.
2. The pathological features and treatment response of NSCLC are affected by genetic and epigenetic profiles, as well as by the cellular origins of the tumours.
3. Target-specific small-molecule inhibitors, such as epidermal growth factor receptor (EGFR) and echinoderm microtubule-associated protein-like 4 (EML4)–anaplastic lymphoma kinase (ALK) inhibitors, have achieved much greater treatment response and survival advantage compared with conventional chemotherapies. However, the treatment response is often short-lived and survival remains limited.
4. Cellular heterogeneity within the tumour milieu influences tumorigenesis, tumour progression and treatment response. The main components of this dynamic microenvironment include vasculature, immune cells, fibroblasts and tumour cell subpopulations.
5. Immune therapies that aim to rejuvenate antitumour immune responses have shown success in early clinical trials. The combination of immunotherapy with other targeted therapies is anticipated in the near future.
6. Data from the bench on criteria for patient stratification and treatment selection are increasingly being translated into clinical practice.

要点翻译：

1. 新一代测序及其他高通量分析技术已开始揭示非小细胞肺癌（NSCLC）存在的多种不同分子和遗传学亚型，并在过去十年中深刻改变了患者的临床评估与治疗模式。
2. 非小细胞肺癌的病理特征及治疗反应受遗传学表观遗传学特征以及肿瘤细胞起源的影响。
3. 相较于传统化疗，靶向小分子抑制剂（如表皮生长因子受体抑制剂、棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶抑制剂）已实现更显著的治疗反应和生存优势。然而治疗反应往往持续时间有限，患者生存期仍不理想。
4. 肿瘤微环境中的细胞异质性影响肿瘤发生、进展及治疗反应。这一动态微环境的主要构成要素包括脉管系统、免疫细胞、成纤维细胞及肿瘤细胞亚群。
5. 旨在激活抗肿瘤免疫应答的免疫疗法在早期临床试验中已取得成效。免疫疗法与其他靶向治疗的联合应用预计在不久的将来得以实现。
6. 基于患者分层与治疗选择标准的实验数据正日益转化为临床实践。

英文摘要：

Non-small-cell lung cancers (NSCLCs), the most common lung cancers, are known to have diverse pathological features. During the past decade, in-depth analyses of lung cancer genomes and signalling pathways have further defined NSCLCs as a group of distinct diseases with genetic and cellular heterogeneity. Consequently, an impressive list of potential therapeutic targets was unveiled, drastically altering the clinical evaluation and treatment of patients. Many targeted therapies have been developed with compelling clinical proofs of concept; however, treatment responses are typically short-lived. Further studies of the tumour microenvironment have uncovered new possible avenues to control this deadly disease, including immunotherapy.

摘要翻译： 

非小细胞肺癌（NSCLC）是最常见的肺癌类型，具有多样的病理特征。过去十年间，对肺癌基因组及信号通路的深入分析进一步将NSCLC界定为一组在遗传和细胞层面均呈异质性的独立疾病。由此，一大批潜在治疗靶点被揭示，彻底改变了患者的临床评估与治疗方式。已开发出许多靶向药物，并具备令人信服的临床概念验证；然而，治疗反应通常短暂。对肿瘤微环境的进一步研究发现了控制这一致命疾病的新途径，包括免疫治疗。

原文链接：

Non-small-cell lung cancers: a heterogeneous set of diseases