靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:Addressing the unmet need in NSCLC progression with advances in second-line therapeutics.
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。
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。
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.
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