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NSCLC 进展中未满足需求的应对:二线治疗的进展

英文原题:Addressing the unmet need in NSCLC progression with advances in second-line therapeutics.

PubMed 2024/11/01(内容时间) Explor Target Antitumor Ther

研究概要

肺癌是全球癌症死亡的首要原因,其中非小细胞肺癌(NSCLC)占 85% 的病例。

中文摘要

肺癌是全球癌症死亡的首要原因,非小细胞肺癌(NSCLC)占病例的85%。尽管免疫治疗和靶向治疗等一线疗法不断进步,耐药仍很常见,因此有效二线治疗存在重大未满足需求。本综述评估晚期或转移性NSCLC当前及新兴的二线治疗选择,重点考察其疗效和改善患者结局的潜力。雷莫芦单抗等抗血管生成药物联合化疗,尤其是多西他赛,已显示中等疗效。靶向特定肿瘤抗原的抗体药物偶联物(ADC)为靶向治疗提供了有前景的途径;嵌合抗原受体(CAR)T细胞疗法和T细胞受体疗法则利用患者免疫系统更有效地对抗癌症。mRNA疫苗虽处于早期阶段,但有望针对癌症特异性抗原诱导强效免疫应答。在此基础上,分子检测的近期进展以及对肿瘤微环境的探索开辟了新的治疗途径,进一步提升NSCLC个体化二线治疗的潜力。ADC和双特异性抗体日益受到关注,但仍需更精准的生物标志物以优化治疗应答。通过液体活检等技术定期监测,可实时追踪EGFR T790M等突变,及时调整治疗。此外,肿瘤微环境中中性粒细胞和巨噬细胞的作用日益受到关注,可能成为治疗切入点,其中Smad3是一个重要靶点。仍需进一步研究药物治疗顺序、毒性管理和生物标志物开发,以改善NSCLC治疗结局。

展开英文摘要原文

Lung cancer is the leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, creating a significant unmet need for effective second-line therapies. This review evaluates current and emerging second-line therapeutic options for advanced or metastatic NSCLC, focusing on their efficacy and potential to improve patient outcomes. Anti-angiogenic drugs like ramucirumab combined with chemotherapy, particularly docetaxel, have shown moderate success. Antibody-drug conjugates (ADCs) targeting specific tumor antigens offer a promising avenue for targeted therapy, while chimeric antigen receptor (CAR)-T cell therapy and T-cell receptor therapy leverage the patient's immune system to combat cancer more effectively. mRNA vaccines, although in early stages, show potential for inducing robust immune responses against cancer-specific antigens. Building on this foundation, recent advancements in molecular testing and the exploration of the tumor microenvironment are opening new therapeutic avenues, further enhancing the potential for personalized second-line treatments in NSCLC. While ADCs and bispecific antibodies are gaining traction, more precise biomarkers are needed to optimize treatment response. Regular monitoring through techniques like liquid biopsies allows real-time tracking of mutations such as EGFR T790M, enabling timely therapeutic adjustments. Additionally, the role of neutrophils and macrophages in the tumor microenvironment is increasingly being recognized as a potential therapeutic avenue, with Smad3 emerging as a key target. Further research into drug sequencing, toxicity management, and biomarker development remains crucial to improving NSCLC treatment outcomes.

论文信息

作者
Wang K、Leyba A、Hsu R
第一作者单位
Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.United States
通讯作者单位
Department of Medicine, Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.United States
文献类型
综述
期刊
Exploration of targeted anti-tumor therapy2024
原文标识
PubMed 39759220 · DOI 10.37349/etat.2024.00277