小细胞肺癌诊疗进展

doi:10.16352/j.issn.1001-6325.2026.08.1149

摘要/Abstract

摘要： 小细胞肺癌(SCLC)是侵袭性强,预后较差的肺部恶性肿瘤。正电子发射计算机断层显像(PET/CT)、人工智能提高了临床分期的准确性,并更为精准地预测疗效。循环肿瘤DNA(ctDNA)和分子分型深化了对SCLC的认知,为精准诊疗奠定了理论基础。治疗方面,免疫检查点抑制剂显著提高了SCLC的预后。同时靶向药物(如DLL3、抗血管、PARP抑制剂、AAK抑制剂等)及新型药物也为SCLC的治疗提供了崭新的视野与思路。本文系统回顾了SCLC近五年在诊疗方面的主要进展,为基础与临床研究提供参考和启示。

关键词: 小细胞肺癌, 分子分型, 免疫治疗, 靶向治疗, Delta样配体3

Abstract: Small cell lung cancer (SCLC) is an aggressive pulmonary malignancy with a poor prognosis. Advances in PET/CT imaging and artificial intelligence have improved the accuracy of clinical staging and enabled more precise prediction of treatment responses. Additionally, circulating tumor DNA analysis and molecular subtyping have deepened our understanding of SCLC, laying a theoretical foundation for precision diagnosis and therapy. Therapeutically, immune checkpoint inhibitors have significantly improved outcomes for SCLC patients. Moreover, targeted therapies—such as DLL3 inhibitors, anti-angiogenic agents, PARP inhibitors, and AAK inhibitors—along with novel therapeutics, are opening new avenues and strategies for SCLC management. This review summarizes the major diagnostic and therapeutic advances in SCLC over the past five years, to provide reference and insights for both basic and clinical research.

Key words: small cell lung cancer, molecular subtyping, immunotherapy, targeted therapy, DLL3

中图分类号:

由婷婷, 唐辉, 宋东峰, 应金蓉, 白春梅. 小细胞肺癌诊疗进展[J]. 基础医学与临床, 2026, 46(8): 1149-1153.

YOU Tingting, TANG Hui, SONG Dongfeng, YING Jinrong, BAI Chunmei. Advances in diagnosis and treatment of small cell lung cancer[J]. Basic & Clinical Medicine, 2026, 46(8): 1149-1153.

参考文献

[1] Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72: 7-33. doi:10.3322/caac.21708.
[2] Zhao J, He Y, Yang X,et al. Assessing treatment outcomes of chemoimmunotherapy in extensive-stage small cell lung cancer: an integrated clinical and radiomics approach[J]. J Immunother Cancer, 2023, 11:e007492. doi:10.1136/jitc-2023-007492.
[3] Song R, Li B, Wang X, et al. Construction and validation of deep learning model for cachexia in extensive-stage small cell lung cancer patients treated with immune checkpoint inhibitors: a multicenter study[J]. Transl Lung Cancer Res, 2024, 13: 2958-2971. doi:10.21037/tlcr-24-543.
[4] Sathekge C, Maes J, Maes A, et al. FDG PET/CT for staging lung carcinoma: An update[J]. Semin Nucl Med, 2025, 55:167-174. doi:10.1053/j.semnuclmed.2025.01.002.
[5] Graabak G, Gronberg BH, Killingberg KT, et al. Effect of FDG PET-CT for staging and radiotherapy planning-a comparison of cohorts from two randomized trials of thoracic radiotherapy in limited-stage SCLC[J]. JTO Clin Res Rep, 2024, 5: 100688. doi:10.1016/j.jtocrr.2024.100688.
[6] Herbreteau G, Langlais A, Greillier L, et al. Circulating tumor DNA as a prognostic determinant in small cell lung cancer patients receiving atezolizumab[J]. J Clin Med, 2020, 9:3861. doi:10.3390/jcm9123861.
[7] Sivapalan L, Iams WT, Belcaid Z, et al. Dynamics of sequence and structural cell-free DNA landscapes in small-cell lung cancer[J]. Clin Cancer Res, 2023, 29: 2310-2323. doi:10.1158/1078-0432.CCR-22-2242.
[8] Megyesfalvi Z, Gay CM, Popper H, et al. Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions[J]. CA Cancer J Clin, 2023, 73: 620-652. doi:10.3322/caac.21785.
[9] Rudin CM, Poirier JT, Byers LA, et al. Molecular subtypes of small cell lung cancer: A synthesis of human and mouse model data[J]. Nat Rev Cancer, 2019, 19: 289-297. doi:10.1038/s41568-019-0133-9.
[10] Baine MK, Hsieh MS, Lai WV, et al. SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: A comprehensive Immunohistochemical and histopathologic characterization[J]. J Thorac Oncol, 2020, 15: 1823-1835. doi:10.1016/j.jtho.2020.09.009.
[11] Baine MK, Febres-Aldana CA, Chang JC, et al. POU2F3 in SCLC: Clinicopathologic and genomic analysis with a focus on its diagnostic utility in neuroendocrine-low SCLC[J]. J Thorac Oncol, 2022, 17: 1109-1121. doi:10.1016/j.jtho.2022.06.004.
[12] Gay CM, Stewart CA, Park EM, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities[J]. Cancer Cell, 2021, 39: 346-360 e347. doi:10.1016/j.ccell.2020.12.014.
[13] Megyesfalvi Z, Barany N, Lantos A, et al. Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: An international multicenter study[J]. J Pathol, 2022, 257: 674-686. doi:10.1002/path.5922.
[14] Higgins KHC, Ross HJ, et al. Concurrent chemoradiation ± atezolizumab (atezo) in limited-stage small cell lung cancer (LS-SCLC): Results of NRG Oncology/Alliance LU005[J]. Int J Radiat Oncol Biol Phys, 2024, 120: S2. doi:10.1016/j.ijrobp.2024.08.013.
[15] Lin S, Zhang Y, Yao J, et al. DB-1314, a novel DLL3-targeting ADC with DNA topoisomerase Ⅰ inhibitor, exhibits promising safety profile and therapeutic efficacy in preclin-ical small cell lung cancer models[J]. J Transl Med, 2024, 22: 766. doi:10.1186/s12967-024-05568-y.
[16] Zhou D, Byers LA, Sable B, et al. Clinical pharmacology profile of AMG 119, the first chimeric antigen receptor T (CAR-T) cell therapy targeting delta-like ligand 3 (DLL3), in patients with relapsed/refractory small cell lung cancer (SCLC)[J]. J Clin Pharmacol, 2024, 64: 362-370. doi:10.1002/jcph.2346.
[17] Liu M, Huang W, Guo Y, et al. CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo[J]. J Leukoc Biol, 2022, 112: 901-911. doi:10.1002/JLB.5MA0122-467R.
[18] Ohe Y, Han B, Nishio M, et al. BEAT-SC: A rando-mized phase Ⅲ study of bevacizumab or placebo in combination with atezolizumab and platinum-based chemother-apy in patients with extensive-stage small cell lung cancer (ES-SCLC)[J]. J Clin Oncol, 2024, 42: 8001. doi:10.1200/JCO.2024.42.16_suppl.8001.
[19] Meador CB, Digumarthy SR, Yeap BY, et al. Phase Ⅰ/Ⅱ investigator-initiated study of olaparib and temozolomide in SCLC: Final analysis and CNS outcomes[J]. Clin Cancer Res, 2025, 31: 25-34. doi:10.1158/1078-0432.CCR-24-2350.
[20] Ran X, Wu BX, Vidhyasagar V, et al. PARP inhibitor radiosensitization enhances anti-PD-L1 immunotherapy through stabilizing chemokine mRNA in small cell lung cancer[J]. Nat Commun, 2025, 16: 2166. doi:10.1038/s41467-025-57257-z.
[21] Chang CP, Yeh TK, Chen CT, et al. Discovery of a long half-life AURKA inhibitor to treat MYC-amplified solid tumors as a monotherapy and in combination with everolimus[J]. Mol Cancer Ther, 2024, 23: 766-779. doi:10.1158/1535-7163.MCT-23-0602.
[22] Owonikoko TK, Niu H, Nackaerts K, et al. Randomized Phase Ⅱ study of paclitaxel plus alisertib versus paclitaxel plus placebo as second-line therapy for SCLC: Primary and correlative biomarker analyses[J]. J Thorac Oncol, 2020, 15: 274-287. doi:10.1016/j.jtho.2019.10.013.
[23] Choudhury NJ, Lai WV, Makhnin A, et al. A Phase Ⅰ/Ⅱ study of valemetostat (DS-3201b), an EZH1/2 inhibitor, in combination with irinotecan in patients with recurrent small-cell lung cancer[J]. Clin Cancer Res, 2024, 30: 3697-3703. doi:10.1158/1078-0432.CCR-23-3383.
[24] Liu H, Xue YC, Deng H, et al. MicroRNA modification of coxsackievirus B3 decreases its toxicity, while retaining oncolytic potency against lung cancer[J]. Mol Ther Oncolytics, 2020, 16: 207-218. doi:10.1016/j.omto.2020.01.002.