文章：

小细胞肺癌：我们知道什么，我们需要知道什么和前进的道路

Small-cell lung cancer: what we know, what we need to know and the path forward

原文发布日期：2017-12-01

DOI: 10.1038/nrc.2017.87

类型: Review Article

开放获取: 否

要点：

1. Small-cell lung cancer (SCLC) is a deadly cancer associated with smoke exposure that has neuroendocrine (NE) cell properties and is pathologically, molecularly, biologically and clinically very different from other lung cancers.
2. While most patients with SCLC respond initially to cytotoxic therapy, almost all tumours recur and are resistant to further therapy. The mortality is very high, resulting in SCLC being designated as a recalcitrant cancer.
3. As tumours in patients with SCLC are seldom resected, tumour materials for research are scant, resulting in a major barrier for translational research.
4. The initiating molecular events are believed to be inactivation of TP53 and RB1, which mainly occurs in NE cells in the respiratory epithelium, although many other genes and signalling pathways are disrupted, especially Notch signalling.
5. For the past 30 years, there have been no important clinical developments or approved, effective conventional or targeted therapies for SCLC. There are no effective methods for early detection or prevention (other than smoking avoidance).
6. However, recently there has been an awakening of interest and funding, resulting in the identification of many promising therapeutic approaches, some of which are already in clinical trials. Thus, while the past has been bleak, the future offers greater promise.

要点翻译：

1. 小细胞肺癌（SCLC）是一种与吸烟相关的致命性癌症，具有神经内分泌细胞特性，在病理学、分子学、生物学和临床特征上与其他肺癌存在显著差异。
2. 虽然大多数小细胞肺癌患者对细胞毒性治疗最初有反应，但几乎所有肿瘤都会复发并对进一步治疗产生耐药。该疾病死亡率极高，因此被定义为顽固性癌症。
3. 由于小细胞肺癌患者的肿瘤很少被切除，可供研究的肿瘤材料极为匮乏，这成为转化研究的主要障碍。
4. 其起始分子事件被认为是TP53和RB1基因失活，主要发生于呼吸道上皮的神经内分泌细胞中，尽管还有许多其他基因和信号通路（尤其是Notch信号通路）也发生异常。
5. 过去30年间，小细胞肺癌领域始终缺乏重要的临床进展，也未有经批准有效的常规或靶向疗法。目前除避免吸烟外，尚无有效的早期检测或预防手段。
6. 然而近期，随着研究关注度和资金投入的显著提升，众多潜力疗法已被识别，其中部分已进入临床试验阶段。由此可见，尽管过往研究进展黯淡，未来却孕育着更大希望。

英文摘要：

Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

摘要翻译： 

小细胞肺癌（SCLC）是一种致命性肿瘤，约占肺癌的15%，在病理、分子、生物学及临床表现上与其他肺癌显著不同。尽管大多数肿瘤表达神经内分泌程序（整合神经与内分泌特性），但重要的一部分肿瘤该程序表达低或缺失。可能的起始分子事件为TP53和RB1的失活，以及包括Notch信号在内的多条信号网络的频繁破坏。SCLC诊断时常已广泛转移，初期对细胞毒治疗有反应，但几乎总是迅速复发并对后续治疗耐药。30年来无重大治疗进展，因此被称为“难治性癌症”。科学研究受限于组织样本匮乏。然而，过去5年全球对SCLC研究重新升温，包括全面分子分析、相关基因工程小鼠模型建立及患者来源异种移植模型的建立。这些研究发现了SCLC新的潜在治疗靶点，推动了新临床试验。因此，尽管过去黯淡，未来更具希望。

原文链接：

Small-cell lung cancer: what we know, what we need to know and the path forward