Cao Zhenyu, Zhu Jiaqi, Chen Xingyou, Chen Zhijian, Wang Weixin, Zhou Youlang, Hua Yuchen, Shi Jiahai, Chen Jianle
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
School of Medicine, Nantong University, Nantong, China.
J Thorac Dis. 2024 Nov 30;16(11):8039-8052. doi: 10.21037/jtd-24-1078. Epub 2024 Nov 15.
Lung cancer continues to be the leading cause of cancer-related deaths globally. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Although targeted therapies and immune checkpoint inhibitors have improved clinical outcomes for NSCLC patients, primary and acquired resistance remain significant obstacles to effective treatment. This review aims to elucidate the molecular mechanisms of NSCLC resistance and explore the potential of nanotechnology-based drug delivery systems in overcoming these resistance barriers.
The research team conducted a comprehensive literature search in PubMed, Cochrane Library, Google Scholar, Embase, Web of Science, China National Knowledge Internet (CNKI), and Wanfang Database, covering the period from January 1st, 2007 to January 1st, 2024.
This review summarizes the molecular mechanisms of NSCLC resistance, including target alterations, bypass signaling pathways, phenotypic transformations, and immunosuppressive mechanisms. It discusses the use of nanotechnology-based drug delivery systems (such as polymeric nanoparticles, liposomes, dendrimers, and inorganic nanoparticles) to overcome various resistance barriers. Additionally, it highlights the role of nanotechnology-based immunotherapeutic strategies in modulating tumor immunity. The review also explores methods for rationally designing combination nanomedicine strategies to address resistance issues at multiple levels, thereby enhancing the effectiveness of NSCLC treatment.
A deep understanding of the mechanisms of NSCLC resistance and the innovative application of nanotechnology-based delivery strategies are crucial for improving patient survival. Rationally designing combination nanomedicine strategies that target multiple resistance mechanisms simultaneously holds promise for overcoming NSCLC resistance and enhancing treatment effectiveness. Further research is needed to investigate the clinical translation of emerging nanotechnologies, providing more effective treatment strategies for NSCLC patients.
肺癌仍然是全球癌症相关死亡的主要原因。非小细胞肺癌（NSCLC）约占肺癌病例的85%。尽管靶向治疗和免疫检查点抑制剂改善了NSCLC患者的临床结局，但原发性和获得性耐药仍然是有效治疗的重大障碍。本综述旨在阐明NSCLC耐药的分子机制，并探索基于纳米技术的药物递送系统在克服这些耐药障碍方面的潜力。
研究团队在PubMed、Cochrane图书馆、谷歌学术、Embase、科学网、中国知网（CNKI）和万方数据库中进行了全面的文献检索，涵盖2007年1月1日至2024年1月1日期间。
本综述总结了NSCLC耐药的分子机制，包括靶点改变、旁路信号通路、表型转化和免疫抑制机制。讨论了使用基于纳米技术的药物递送系统（如聚合物纳米颗粒、脂质体、树枝状大分子和无机纳米颗粒）来克服各种耐药障碍。此外，强调了基于纳米技术的免疫治疗策略在调节肿瘤免疫中的作用。该综述还探讨了合理设计联合纳米药物策略以在多个层面解决耐药问题的方法，从而提高NSCLC治疗的有效性。
深入了解NSCLC耐药机制以及基于纳米技术的递送策略的创新应用对于提高患者生存率至关重要。同时针对多种耐药机制合理设计联合纳米药物策略有望克服NSCLC耐药并提高治疗效果。需要进一步研究新兴纳米技术的临床转化，为NSCLC患者提供更有效的治疗策略。
