Wang Kinsley, Leyba Alexis, Hsu Robert
Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA.
Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Explor Target Antitumor Ther. 2024;5(6):1297-1320. doi: 10.37349/etat.2024.00277. Epub 2024 Nov 1.
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.
肺癌是全球癌症死亡的主要原因，其中非小细胞肺癌（NSCLC）占病例的85%。尽管免疫疗法和靶向疗法等一线治疗取得了进展，但对这些治疗的耐药性很常见，这就产生了对有效二线疗法的重大未满足需求。本综述评估了晚期或转移性NSCLC的当前和新兴二线治疗选择，重点关注它们的疗效和改善患者预后的潜力。像雷莫西尤单抗这样的抗血管生成药物与化疗（尤其是多西他赛）联合使用已取得了一定的成功。靶向特定肿瘤抗原的抗体药物偶联物（ADC）为靶向治疗提供了一条有前景的途径，而嵌合抗原受体（CAR）-T细胞疗法和T细胞受体疗法则利用患者的免疫系统更有效地对抗癌症。mRNA疫苗虽然尚处于早期阶段，但显示出诱导针对癌症特异性抗原的强大免疫反应的潜力。在此基础上，分子检测的最新进展和对肿瘤微环境的探索正在开辟新的治疗途径，进一步增强了NSCLC个性化二线治疗的潜力。虽然ADC和双特异性抗体越来越受到关注，但需要更精确的生物标志物来优化治疗反应。通过液体活检等技术进行定期监测，可以实时跟踪EGFR T790M等突变，从而及时进行治疗调整。此外，中性粒细胞和巨噬细胞在肿瘤微环境中的作用越来越被认为是一条潜在的治疗途径，Smad3成为一个关键靶点。对药物序贯、毒性管理和生物标志物开发的进一步研究对于改善NSCLC治疗结果仍然至关重要。
