Small-cell lung cancer.
Small-cell lung cancer.
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DOI：
10.1038/s41572-020-00235-0
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发表时间：
2021-01-14
期刊：
影响因子：
--
通讯作者：
Sage J
中科院分区：
文献类型：
--
作者：
Rudin CM;Brambilla E;Faivre-Finn C;Sage J
小细胞肺癌(SCLC)约占所有肺癌的15%，具有异常高的增殖率、强烈的早期转移倾向和不良的预后。小细胞肺癌与烟草致癌物的接触密切相关。大多数患者在确诊时都有转移性疾病，只有三分之一的患者有早期疾病，可以通过潜在的多种疗法治愈。小细胞肺癌的基因组图谱显示广泛的染色体重排和高突变负担，几乎总是包括肿瘤抑制基因TP53和RB1的功能失活。对人类小细胞肺癌和小鼠模型的分析已经根据主要转录调控因子的相对表达确定了疾病的亚型，并揭示了肿瘤内的实质性异质性。这种异质性的某些方面与肿瘤的演变、转移和获得性治疗耐药有关。尽管小细胞肺癌治疗的临床进展是出了名的慢，但对疾病生物学的更好理解已经发现了可能适用于靶向治疗方法的新的脆弱性。最近将免疫检查点阻断引入小细胞肺癌患者的治疗提供了新的希望，一小部分患者获得了长期的好处。针对那些最有可能有反应的患者进行定向治疗的战略，以及将有效的抗肿瘤免疫的持久益处扩大到更大比例的患者的战略是迫切需要的，目前正在积极探索。
Small-cell lung cancer (SCLC) represents about 15% of all lung cancers and is marked by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis, with only one-third having earlier-stage disease that is amenable to potentially curative multimodality therapy. Genomic profiling of SCLC reveals extensive chromosomal rearrangements and a high mutation burden, almost always including functional inactivation of the tumour suppressor genes TP53 and RB1. Analyses of both human SCLC and murine models have defined subtypes of disease based on the relative expression of dominant transcriptional regulators and have also revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. Although clinical progress in SCLC treatment has been notoriously slow, a better understanding of the biology of disease has uncovered novel vulnerabilities that might be amenable to targeted therapeutic approaches. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is offering new hope, with a small subset of patients deriving prolonged benefit. Strategies to direct targeted therapies to those patients who are most likely to respond and to extend the durable benefit of effective antitumour immunity to a greater fraction of patients are urgently needed and are now being actively explored.
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DOI：
10.1016/j.jtho.2017.09.1951
发表时间：
2018-01
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Almodovar K;Iams WT;Meador CB;Zhao Z;York S;Horn L;Yan Y;Hernandez J;Chen H;Shyr Y;Lim LP;Raymond CK;Lovly CM
通讯作者：
Lovly CM
影响因子：
8
作者：
Burger, M;Glodek, A;Burger, JA
通讯作者：
Burger, JA
影响因子：
45.3
作者：
BRAMBILLA, E;MORO, D;BRAMBILLA, C
通讯作者：
BRAMBILLA, C
DOI：
10.1016/j.jtcvs.2004.08.022
发表时间：
2005-01-01
影响因子：
6
作者：
Brock, MV;Hooker, CM;Yang, SC
通讯作者：
Yang, SC
影响因子：
11.5
作者：
Canadas, Israel;Rojo, Federico;Arriola, Edurne
通讯作者：
Arriola, Edurne