Ouyang Wei, Xu Ziyao, Guan Shaoyu, Hu Yang, Gou Xiaoxue, Liu Zhe, Guo Wei, Huang Ye, Zhang Lifen, Zhang Xingmei, Li Tian, Yang Bin
Hubei Cancer Hospital, Tongji Medical College, Huazhong University of science and Technology, Wuhan, Hubei, China.
Department of General Surgery, The first Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing 100853, China.
Int J Biol Sci. 2025 Jan 20;21(3):1322-1341. doi: 10.7150/ijbs.105973. eCollection 2025.
Small cell lung cancer (SCLC) is an intractable disease with rapid progression and high mortality, presenting a persistent obstacle impeding clinical management. Although recent advancements in immunotherapy have enhanced the response rates of platinum-based chemotherapy regimens, the emergence of acquired resistance invariably leads to recurrence and metastasis. Consequently, there is an urgent necessity to explore novel therapeutic targets and optimize existing treatment strategies. This article comprehensively reviews the currently available therapeutic modalities for SCLC. It delves into the immunologic prognostic implications by analyzing selected immune-related signatures. Moreover, it conducts an in-depth exploration of the molecular subtyping of SCLC and the associated molecular pathways to identify potential therapeutic targets. Specifically, the focus is on clinical interventions targeting delta-like ligand 3 (DLL3), elucidating its resistance mechanisms and demonstrating its notable antitumor efficacy. Furthermore, the study examines the mechanisms of chimeric antigen receptor (CAR) T and antibody-drug conjugate (ADC), covering resistance issues and strategies for optimizing resistance management, with particular emphasis being placed on analyzing the prospects and clinical value of CAR T therapy in the context of SCLC. Moreover, the effectiveness of poly ADP-ribose polymerase and ataxia telangiectasia and rad3/checkpoint kinase 1 inhibitors is discussed and underscores the advantages of combining these inhibitors with standard chemotherapy to combat chemoresistance and enhance the antitumor effects of immunotherapies. Overall, this study investigates emerging strategies for targeted therapies and optimized combination regimens to overcome resistance in SCLC and highlights future strategies for new therapeutic technologies for SCLC.
小细胞肺癌（SCLC）是一种进展迅速且死亡率高的难治性疾病，一直是阻碍临床治疗的难题。尽管免疫疗法的最新进展提高了铂类化疗方案的缓解率，但获得性耐药的出现总是导致复发和转移。因此，迫切需要探索新的治疗靶点并优化现有治疗策略。本文全面综述了目前可用于治疗SCLC的方法。通过分析选定的免疫相关特征，深入探讨了免疫预后意义。此外，对SCLC的分子亚型及相关分子途径进行了深入研究，以确定潜在的治疗靶点。具体而言，重点是针对δ样配体3（DLL3）的临床干预，阐明其耐药机制并证明其显著的抗肿瘤疗效。此外，该研究还考察了嵌合抗原受体（CAR）T细胞和抗体药物偶联物（ADC）的作用机制，涵盖耐药问题及优化耐药管理的策略，特别强调在SCLC背景下分析CAR T细胞疗法的前景和临床价值。此外，还讨论了聚ADP核糖聚合酶以及共济失调毛细血管扩张症和rad3/检查点激酶1抑制剂的有效性，并强调将这些抑制剂与标准化疗联合使用以对抗化疗耐药性和增强免疫疗法抗肿瘤效果的优势。总体而言，本研究探讨了针对SCLC的靶向治疗和优化联合方案以克服耐药性的新兴策略，并突出了SCLC新治疗技术的未来策略。
