Cell-by-Cell: Unlocking Lung Cancer Pathogenesis.
Cell-by-Cell: Unlocking Lung Cancer Pathogenesis.
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作者：
肺癌筛查的进展导致越来越需要早期干预策略，以扩大被诊断为头号癌症杀手的患者队列。这些努力在很大程度上依赖于在细胞水平上对影响正常肺上皮及其周围微环境的致病过程的深入理解。最近，单细胞测序方法的进展已经解码了以前难以理解的肺恶性过程的复杂性。在这里，我们回顾了基于单细胞的方法的一些主要贡献，这些方法用于增强我们对非小细胞肺癌（更具体地说，肺腺癌）的了解。我们专注于如何在细胞水平上研究肺腺癌，继续解开一个未知的肿瘤内异质性水平，确定在肿瘤开始的心脏可塑性细胞状态，并阐明恶化前进展的复杂生物学，从而指导这种致命疾病的临床管理的新方法。对于肺癌，细胞轨迹和命运受到细胞内在和外在因素的强烈修剪。在过去的几十年里，综合分子和基因组方法的结合，以及相关临床前模型的使用，增强的显微解剖技术，罕见癌前病变和周围组织的分析，以及多区域肿瘤测序，都为肺癌的早期生物学和演变提供了深入的见解。单细胞测序技术的出现彻底改变了我们以前所未有的分辨率询问这些相同模型，组织和队列的能力。肺癌发病机制的单细胞追踪正在改变我们对疾病演变过程中上皮微环境线索和串扰的作用和后果的理解。通过关注非小细胞肺癌，特别是肺腺癌亚型，本文旨在总结我们的知识基础的肿瘤细胞的起源和肿瘤免疫动力学，主要是由单细胞分析肺腺癌标本在疾病发病机制的各个阶段和相关的动物模型。该综述将提供一个概述，最近的报告是如何重写的机制的细节谱系可塑性和肿瘤内的异质性在一个放大的规模由于早期到晚期肺腺癌的单细胞研究。单细胞技术的未来进展，加上对微量罕见临床组织和新型动物模型的分析，预计将有助于改变我们对不同微事件如何引发宏观后果的理解，从而显着推进肺癌演变的基本基因组和分子知识如何转化为早期检测和预防这种致命疾病的成功靶点。
Advances in lung cancer screening have led to a growing need for early intervention strategies for the expanding cohort of patients being diagnosed with the number one cancer killer. Such efforts heavily rely on an in-depth understanding of the pathogenic processes affecting normal lung epithelium and its surrounding microenvironment at the cellular level. More recently, advances in single-cell sequencing approaches have decoded much of the previously elusive complexity of lung malignant processes. Here, we review some of the major contributions of single-cell-based approaches that were employed to enhance our understanding of non-small cell lung cancers, and more specifically, lung adenocarcinomas. We focus on how studying lung adenocarcinomas at a cell-by-cell level continues to unravel an unbeknownst level of intratumor heterogeneity, identify plastic cell states at the heart of tumor inception, and elucidate the complex biology of premalignant progression, thus guiding novel approaches for clinical management of this deadly disease. For lung cancers, cellular trajectories and fates are strongly pruned by cell intrinsic and extrinsic factors. Over the past couple of decades, the combination of comprehensive molecular and genomic approaches, as well as the use of relevant pre-clinical models, enhanced micro-dissection techniques, profiling of rare preneoplastic lesions and surrounding tissues, as well as multi-region tumor sequencing, have all provided in-depth insights into the early biology and evolution of lung cancers. The advent of single-cell sequencing technologies has revolutionized our ability to interrogate these same models, tissues, and cohorts at an unprecedented resolution. Single-cell tracking of lung cancer pathogenesis is now transforming our understanding of the roles and consequences of epithelial-microenvironmental cues and crosstalk during disease evolution. By focusing on non-small lung cancers, specifically lung adenocarcinoma subtype, this review aims to summarize our knowledge base of tumor cells-of-origin and tumor–immune dynamics that have been primarily fueled by single-cell analysis of lung adenocarcinoma specimens at various stages of disease pathogenesis and of relevant animal models. The review will provide an overview of how recent reports are rewriting the mechanistic details of lineage plasticity and intra-tumor heterogeneity at a magnified scale thanks to single-cell studies of early- to late-stage lung adenocarcinomas. Future advances in single-cell technologies, coupled with analysis of minute amounts of rare clinical tissues and novel animal models, are anticipated to help transform our understanding of how diverse micro-events elicit macro-scale consequences, and thus to significantly advance how basic genomic and molecular knowledge of lung cancer evolution can be translated into successful targets for early detection and prevention of this lethal disease.
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正常细胞的基因组测序揭示了发育谱系和突变过程。
影响因子：
64.8
作者：
Behjati, Sam;Huch, Meritxell;van Boxtel, Ruben;Karthaus, Wouter;Wedge, David C.;Tamuri, Asif U.;Martincorena, Inigo;Petljak, Mia;Alexandrov, Ludmil B.;Gundem, Gunes;Tarpey, Patrick S.;Roerink, Sophie;Blokker, Joyce;Maddison, Mark;Mudie, Laura;Robinson, Ben;Nik-Zainal, Serena;Campbell, Peter;Goldman, Nick;van de Wetering, Marc;Cuppen, Edwin;Clevers, Hans;Stratton, Michael R.
通讯作者：
Stratton, Michael R.
影响因子：
8
作者：
Cheung WK;Nguyen DX
通讯作者：
Nguyen DX
影响因子：
16.6
作者：
Angelidis, Ilias;Simon, Lukas M.;Schiller, Herbert B.
通讯作者：
Schiller, Herbert B.
影响因子：
168.9
作者：
Goldstraw, Peter;Ball, David;Shepherd, Frances A.
通讯作者：
Shepherd, Frances A.
DOI：
10.1126/science.1253462
发表时间：
2014-10-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Bruin EC;McGranahan N;Mitter R;Salm M;Wedge DC;Yates L;Jamal-Hanjani M;Shafi S;Murugaesu N;Rowan AJ;Grönroos E;Muhammad MA;Horswell S;Gerlinger M;Varela I;Jones D;Marshall J;Voet T;Van Loo P;Rassl DM;Rintoul RC;Janes SM;Lee SM;Forster M;Ahmad T;Lawrence D;Falzon M;Capitanio A;Harkins TT;Lee CC;Tom W;Teefe E;Chen SC;Begum S;Rabinowitz A;Phillimore B;Spencer-Dene B;Stamp G;Szallasi Z;Matthews N;Stewart A;Campbell P;Swanton C
通讯作者：
Swanton C