Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?
Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes?
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DOI：
10.1016/j.jtho.2016.01.012
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发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Hirsch FR
中科院分区：
文献类型：
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作者：
Bunn PA Jr;Minna JD;Augustyn A;Gazdar AF;Ouadah Y;Krasnow MA;Berns A;Brambilla E;Rekhtman N;Massion PP;Niederst M;Peifer M;Yokota J;Govindan R;Poirier JT;Byers LA;Wynes MW;McFadden DG;MacPherson D;Hann CL;Farago AF;Dive C;Teicher BA;Peacock CD;Johnson JE;Cobb MH;Wendel HG;Spigel D;Sage J;Yang P;Pietanza MC;Krug LM;Heymach J;Ujhazy P;Zhou C;Goto K;Dowlati A;Christensen CL;Park K;Einhorn LH;Edelman MJ;Giaccone G;Gerber DE;Salgia R;Owonikoko T;Malik S;Karachaliou N;Gandara DR;Slotman BJ;Blackhall F;Goss G;Thomas R;Rudin CM;Hirsch FR
小细胞肺癌（SCLC）是肺癌的四种主要组织学类型之一。近年来，发达国家 SCLC 的发病率有所下降，可能是由于卷烟成分的变化。在美国，SCLC 估计约占新诊断肺癌的 16%，相当于每年约 35,000 个新病例。在欠发达国家，SCLC 病例的百分比可能更高。 SCLC 存在大量遗传改变，包括抑癌基因的改变、拷贝数增加以及转录因子、参与染色质修饰的酶、受体酪氨酸激酶及其下游信号成分的其他体细胞突变。 1 SCLC 具有很高的早期扩散倾向，并且对细胞毒性化疗具有较高的初始反应性，通常随后会迅速产生耐药性。因此，基本上任何阶段的所有患者都接受依托泊苷与顺铂或卡铂的双重组合。对于罕见的无淋巴结转移的患者，化疗可以在手术后进行，而对于有淋巴结转移且无远处转移的患者，通常会同时进行化疗和胸部放疗。不幸的是，这些疗法的效果持续时间很短，并且在大多数情况下没有治愈作用，5 年生存率低于 7%。过去 30 年来没有出现重大治疗进展。 2 自1996年批准拓扑替康以来，美国食品和药物管理局(FDA)尚未批准任何新药用于治疗SCLC患者。 3 由于这些原因，SCLC 在美国被宣布为“顽固性”癌症。然而，由于对 SCLC 生物学和分子生物学理解的最新进展，包括靶向治疗在内的大量治疗机会存在，部分原因在于新的模型系统。
Small cell lung cancer (SCLC) is one of the four major histological types of lung cancer. The incidence of SCLC in developed countries has declined in recent years, presumably because of changes in cigarette composition. In the United States, SCLC is estimated to represent approximately 16% of new lung cancer diagnoses, which equates to approximately 35,000 new cases annually. In underdeveloped countries the percentage of SCLC cases may be higher. SCLC presents with a very large number of genetic alterations, including alterations of tumor suppressor genes, and copy number gains and other somatic mutations in transcription factors, enzymes involved in chromatin modification, and receptor tyrosine kinases and their downstream signaling components. 1 SCLC has a high propensity for early spread and a high initial responsiveness to cytotoxic chemotherapy that is usually followed by rapid development of resistance. Thus, essentially all patients in any stage receive a doublet combination of etoposide with cisplatin or carboplatin. For the rare patient without nodal involvement, the chemotherapy may follow surgery, and for the patient with nodal disease without distant metastases, a combination of chemotherapy with chest radiotherapy is usually given concurrently. Unfortunately, the duration of effect of these therapies is short and they are not curative in most instances, with 5-year survival rates less than 7%. No major treatment advances have occurred over the past 30 years. 2 Since the approval of topotecan in 1996, the US Food and Drug Administration (FDA) has not approved any new drugs for the treatment of patients with SCLC. 3 For these reasons SCLC was declared a “recalcitrant” cancer in the United States. However, considerable therapeutic opportunities, including targeted therapies, exist because of recent developments in understanding of the biology and molecular biology of SCLC that are in part due to the new model systems.