Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.

中文翻译：

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小细胞肺癌的临床见解：肿瘤异质性、诊断、治疗和未来方向

小细胞肺癌（SCLC）具有生长快、转移能力强的特点。它与烟草致癌物有很强的流行病学和生物学联系。尽管大多数 SCLC 表现出神经内分泌特征，但肿瘤的一个重要子集缺乏这些特性。SCLC 的基因组分析揭示了遗传不稳定性、肿瘤抑制基因TP53和RB1几乎普遍失活以及高突变负担。由于早期转移，只有一小部分患者适合进行根治性肺切除术，这些患者需要辅助铂依托泊苷化疗。因此，绝大多数患者目前正在接受放化疗联合或不联合免疫治疗。对于疾病局限于胸部的患者，标准治疗包括胸部放疗和同步铂依托泊苷化疗。患有转移性（广泛期）疾病的患者接受铂-依托泊苷化疗加抗程序性死亡配体 1 单克隆抗体免疫疗法的组合治疗。尽管 SCLC 最初对铂类化疗非常敏感，但由于耐药性的发展，这些反应是短暂的。近年来，作者见证了对该疾病的生物学认识的不断加快，导致 SCLC 分类方案的重新定义。这种关于 SCLC 分子亚型的新兴知识有可能确定独特的治疗漏洞。将这些新发现与 SCLC 生物学和临床管理的当前知识相结合，可能会导致 SCLC 患者护理取得前所未有的进步。在此，作者概述了 SCLC 的多模式临床方法，特别重点阐述了 SCLC 研究的最新进展如何加速临床开发。