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Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions.
文献信息
| DOI | 10.3322/caac.21785 |
|---|---|
| PMID | 37329269 |
| 期刊 | CA: a cancer journal for clinicians |
| 影响因子 | 232.4 |
| JCR 分区 | Q1 |
| 发表年份 | 2023 |
| 被引次数 | 161 |
| 关键词 | 化疗、诊断、免疫疗法、分子亚型、小细胞肺癌 |
| 文献类型 | Journal Article, Review, Research Support, Non-U.S. Gov't |
| ISSN | 0007-9235 |
| 页码 | 620-652 |
| 期号 | 73(6) |
| 作者 | Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome |
一句话小结
小细胞肺癌（SCLC）因其快速生长和高度转移性而具有严重的临床挑战，尽管对铂类化疗最初反应良好，但耐药性使得疗效短暂。近期对SCLC生物学的深入研究促使其分类方案重新定义，这可能揭示新的治疗靶点，为患者的临床管理和护理带来重大进展。
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摘要
小细胞肺癌（SCLC）以其快速生长和高度转移能力为特征。它与烟草致癌物具有强烈的流行病学和生物学联系。尽管大多数小细胞肺癌表现出神经内分泌特征，但有一重要亚型的肿瘤缺乏这些特性。小细胞肺癌的基因组分析显示出遗传不稳定性，几乎普遍存在肿瘤抑制基因TP53和RB1的失活，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治愈性肺切除手术，这些患者需要辅助铂类-依托泊苷化疗。因此，目前绝大多数患者接受化学放疗，可能伴随或不伴随免疫疗法。在疾病局限于胸腔的患者中，标准治疗包括胸部放疗和同步铂类-依托泊苷化疗。对于转移性（广泛期）疾病患者，治疗方案为铂类-依托泊苷化疗与抗程序性死亡配体1单克隆抗体免疫疗法的联合应用。尽管小细胞肺癌最初对基于铂的化疗反应良好，但由于耐药性的出现，这些反应是短暂的。近年来，作者见证了对该疾病生物学洞察的加速发展，这导致了小细胞肺癌分类方案的重新定义。对小细胞肺癌分子亚型的新认识可能会揭示独特的治疗脆弱性。将这些新发现与当前的小细胞肺癌生物学和临床管理知识相结合，可能会为小细胞肺癌患者护理带来前所未有的进展。在此，作者对小细胞肺癌的多模式临床方法进行了概述，特别关注最近的小细胞肺癌研究进展如何加速临床发展。
英文摘要
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.
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主要研究问题
- 小细胞肺癌的不同分子亚型在治疗选择上有什么具体影响？
- 在小细胞肺癌的早期诊断中，除了传统影像学检查外，还有哪些新兴的生物标志物或检测方法？
- 针对小细胞肺癌的耐药机制，目前有哪些研究进展和潜在的解决方案？
- 小细胞肺癌的化疗和免疫疗法联合使用时，如何评估疗效和副作用？
- 在未来的研究方向中，有哪些新兴疗法或技术可能会改变小细胞肺癌的治疗格局？
核心洞察
1. 研究背景和目的
小细胞肺癌（SCLC）是一种生长迅速且具有高度转移能力的恶性肿瘤，主要与烟草致癌物相关。尽管大多数SCLC表现出神经内分泌特征，但部分肿瘤缺乏这些特性。由于其早期转移的特性，大部分患者无法接受根治性手术，因此本研究旨在探讨SCLC的肿瘤异质性、诊断、治疗方法及未来研究方向，以期为临床提供新的见解。
2. 主要方法和发现
本研究通过基因组分析揭示了SCLC的遗传不稳定性，几乎普遍出现肿瘤抑制基因TP53和RB1的失活，以及高突变负荷。对于局限于胸部的患者，标准治疗方案包括胸部放疗和铂类-依托泊苷化疗；而对于转移性（广泛期）疾病患者，则采用铂类-依托泊苷化疗加免疫疗法（抗程序性死亡配体1单克隆抗体）。尽管SCLC对铂类化疗初期反应良好，但由于耐药性的出现，这种反应通常是短暂的。近年来，SCLC的生物学研究进展迅速，使得SCLC的分类方案得到了重新定义，并为个性化治疗提供了可能的靶点。
3. 核心结论
本研究表明，SCLC的肿瘤异质性和遗传特征对治疗方案的制定有重要影响。新的分子亚型的发现为SCLC的精准治疗提供了潜在的治疗脆弱性和靶向机制。尽管现有的化疗和放疗方案在短期内有效，但长期的耐药性问题仍需进一步研究和解决。
4. 研究意义和影响
本研究的意义在于整合了SCLC最新的生物学发现与临床管理知识，强调了多模态治疗的重要性，并为未来的临床研究指明了方向。这些新发现不仅有助于改善SCLC患者的治疗效果，还可能推动个性化医疗的发展，从而提高患者的生存率和生活质量。通过加速新疗法的临床开发，未来有望在SCLC的治疗领域取得突破性进展。
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