Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75230-8593, USA.
Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75230-8593, USA.
Nat Rev Cancer. 2017 Dec;17(12):725-737. doi: 10.1038/nrc.2017.87. Epub 2017 Oct 27.
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.
小细胞肺癌（SCLC）是一种致命的肿瘤，约占肺癌的 15%，在病理、分子、生物学和临床方面与其他肺癌有很大的不同。虽然大多数肿瘤表达神经内分泌程序（整合神经和内分泌特性），但重要的肿瘤亚群表达这种程序的水平较低或缺失。可能的起始分子事件是 TP53 和 RB1 的失活，以及包括 Notch 信号通路在内的几个信号通路的频繁中断。SCLC 在诊断时通常广泛转移，最初对细胞毒性治疗有反应，但几乎总是迅速复发，并对进一步的治疗产生耐药性。30 年来，没有重要的治疗临床进展，导致 SCLC 被指定为“难治性癌症”。科学研究受到组织可用性不足的阻碍。然而，在过去的 5 年中，全球范围内对 SCLC 的研究出现了复苏，包括全面的分子分析、相关基因工程小鼠模型的开发以及患者来源的异种移植物的建立。这些研究发现了 SCLC 的新的潜在治疗弱点，并因此开展了新的临床试验。因此，虽然过去黯淡无光，但未来充满希望。
