综述：小细胞肺癌治疗的新策略

SCI 1 January 2022

Emerging Strategies for the Treatment of Small Cell Lung Cancer, A Review

(JAMA Oncology, IF: 33.006)

W. Jeffrey Petty, Luis Paz-Ares

CORRESPONDENCE TO: lpazaresr@seom.org

IMPORTANCE 重要性  

Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking.

小细胞肺癌（SCLC）是一种侵袭性疾病，其特征是快速生长和早期转移。患者通常对初始化疗有反应，但很快会复发，导致长期预后不良。历史上，大幅提高生存率的治疗创新一直有限，缺乏可靠的预测性生物标志物。

OBSERVATIONS 观察

This review examines the biologic characteristics of SCLC, the current treatment landscape, and ongoing efforts to identify novel therapeutic targets. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Recently, immunotherapy-based regimens have become available for the management of SCLC, with 2 programmed cell death 1 ligand 1 inhibitors approved in combination with chemotherapy for first-line treatment of extensive-stage disease. For second-line treatment, a novel alkylating agent, lurbinectedin, which inhibits oncogenic transcription, has been approved for use in patients with metastatic SCLC. Furthermore, a wide variety of therapies and innovative combination regimens are being continuously evaluated. Potential therapeutic strategies, including aurora kinase A inhibitors, polyadenosine diphosphate-ribose polymerase inhibitors, ataxia telangiectasia and Rad3-related inhibitors, cyclin-dependent kinase 7 inhibitors, delta-like protein 3 agents, antiganglioside agents, CD47 inhibitors, and lysine-specific histone demethylase 1a inhibitors, are also being examined.

本文概述了SCLC的生物学特征、当前的治疗前景以及正在进行的确定新治疗靶点的努力。正在进行的研究促进了对SCLC分子类别和免疫微环境的理解，这反过来有助于改善疾病分类和分期。最近，基于免疫疗法的方案已可用于SCLC的治疗，2种程序性细胞死亡1配体1抑制剂与化疗联合获批用于广泛期疾病的一线治疗。对于二线治疗，一种新的烷化剂，即抑制致癌转录的Lurbinectedin，已被批准用于转移性小细胞肺癌患者。此外，各种疗法和联合创新疗法正在不断评估中。潜在的治疗策略，包括极光激酶A抑制剂、聚腺苷二磷酸核糖聚合酶抑制剂、共济失调毛细血管扩张症和Rad3相关抑制剂、细胞周期蛋白依赖性激酶7抑制剂、delta样蛋白3抑制剂、抗神经节苷脂剂、CD47抑制剂和赖氨酸特异性组蛋白去甲基化酶1a抑制剂等也正在研究中。

CONCLUSIONS AND RELEVANCE 结论和相关性

Therapeutic optimization of SCLC remains a challenge, but recent trial results and drug approvals are encouraging. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC.

SCLC的治疗优化仍然是一个挑战，但最近的试验结果和药物批准情形令人鼓舞。研究进展揭示了有关该疾病生物学特征的关键信息，这可能促使脆弱性识别和开发新的治疗方法。后续研究聚焦于识别生物标志物和评估创新疗法，对于改善SCLC患者的治疗结果至关重要。

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