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小细胞肺癌创新靶向治疗的进展机遇与探索

英文原题:Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer.

查看英文原题

Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer.

PubMed 2025/01/20(内容时间) Int J Biol Sci Q1 · IF 11.7(JCR 2025)

研究概要

小细胞肺癌(SCLC)是一种难以治愈的疾病,进展迅速、死亡率高,是临床管理中持续存在的障碍。

中文摘要

小细胞肺癌(SCLC)是一种难以治愈的疾病,进展迅速、死亡率高,是临床管理中持续存在的障碍。尽管近年来免疫治疗的进展提高了铂类化疗方案的缓解率,但获得性耐药的出现不可避免地导致复发和转移。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SCLC的治疗方式。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的分子分型及相关分子通路进行了深入探索,以确定潜在的治疗靶点。具体而言,重点关注靶向delta样配体3(DLL3)的临床干预,阐明其耐药机制并展示其显著的抗肿瘤疗效。此外,本研究还探讨了嵌合抗原受体(CAR)T细胞和抗体药物偶联物(ADC)的机制,涵盖耐药问题及优化耐药管理的策略,特别着重分析CAR T疗法在SCLC背景下的前景和临床价值。此外,还讨论了聚ADP核糖聚合酶和共济失调毛细血管扩张症及Rad3相关/检查点激酶1抑制剂的有效性,并强调了将这些抑制剂与标准化疗联合使用以克服化疗耐药和增强免疫治疗抗肿瘤效果的优势。总体而言,本研究探讨了针对SCLC耐药性的靶向治疗和优化联合方案的新兴策略,并强调了SCLC新治疗技术的未来策略。

展开英文摘要原文

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.

论文信息

作者
Ouyang W、Xu Z、Guan S、Hu Y、Gou X、Liu Z、Guo W、Huang Y
单位
Hubei Cancer Hospital, Tongji Medical College, Huazhong University of science and Technology, Wuhan, Hubei, China.China
文献类型
综述
期刊
International journal of biological sciences2025
原文标识
PubMed 39897044 · DOI 10.7150/ijbs.105973