Departments of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
School of Medicine MD Program, Case Western Reserve University, Cleveland, OH, 44106, USA.
Exp Mol Med. 2019 Dec 12;51(12):1-13. doi: 10.1038/s12276-019-0349-5.
Small-cell lung cancer (SCLC) remains the deadliest of all the lung cancer types. Its high mortality is largely attributed to the invariable development of resistance to standard chemo/radiotherapies, which have remained unchanged for the past 30 years, underscoring the need for new therapeutic approaches. The discovery of molecular targets for chemoprevention and treatment has been hampered by the poor understanding of SCLC progression. In recent years, comprehensive omics-based analyses have led to the discovery of recurrent alterations in patient tumors, and functional studies using genetically engineered mouse models and patient-derived tumor models have provided information about the alterations critical for SCLC pathogenesis. Defining the somatic alterations scattered throughout the SCLC genome will help to understand the underlying mechanism of this devastating disease and pave the way for the discovery of therapeutic vulnerabilities associated with the genomic alterations.
小细胞肺癌（SCLC）仍然是所有肺癌类型中最致命的。其高死亡率主要归因于对标准化疗/放疗的不可避免的耐药性发展，在过去 30 年中一直没有改变，这突显了需要新的治疗方法。由于对 SCLC 进展的了解不足，化学预防和治疗的分子靶标的发现受到了阻碍。近年来，基于组学的综合分析导致发现了患者肿瘤中反复出现的改变，使用基因工程小鼠模型和患者来源的肿瘤模型进行的功能研究提供了有关 SCLC 发病机制关键改变的信息。确定分散在 SCLC 基因组中的体细胞改变将有助于了解这种破坏性疾病的潜在机制，并为发现与基因组改变相关的治疗弱点铺平道路。
