Background: The persistence of chemotherapy-resistant and dormant cancer cells remains a critical challenge in the treatment of lung cancer. Objectives: This review focuses on non-small cell lung cancer and small cell lung cancer, examining the complex mechanisms that drive treatment resistance.Methods: This review analyzed current studies on chemotherapy resistance in NSCLC and SCLC, focusing on tumor microenvironment, genetic mutations, cancer cell heterogeneity, and emerging therapies.Results: Conventional chemotherapy and targeted therapies, such as tyrosine kinase inhibitors, often fail due to factors including the tumor microenvironment, genetic mutations, and cancer cell heterogeneity. Dormant cancer cells, which can remain undetected in a quiescent state for extended periods, pose a significant risk of recurrence upon reactivation. These cells, along with intrinsic resistance mechanisms, greatly complicate treatment efforts. Understanding these pathways is crucial for the development of more effective therapies. Emerging strategies, including combination therapies that target multiple pathways, are under investigation to improve treatment outcomes. Innovative approaches, such as antibody–drug conjugates and targeted protein degradation, offer promising solutions by directly delivering cytotoxic agents to cancer cells or degrading proteins that are essential for cancer survival. The lung cancer organoid model shows substantial promise to advance both research and clinical applications in this field, enhancing the ability to study resistance mechanisms and develop personalized treatments. The integration of current research underscores the need for continuous innovation in treatment modalities.Conclusions: Personalized strategies that combine novel therapies with an in-depth understanding of tumor biology are essential to overcome the challenges posed by treatment-resistant and dormant cancer cells in lung cancer. A multifaceted approach has the potential to significantly improve patient outcomes.
背景：化疗耐药与休眠癌细胞的持续存在是肺癌治疗中的关键挑战。 目的：本综述聚焦于非小细胞肺癌与小细胞肺癌，探讨驱动治疗耐药性的复杂机制。 方法：通过分析当前关于非小细胞肺癌和小细胞肺癌化疗耐药的研究，重点关注肿瘤微环境、基因突变、癌细胞异质性及新兴治疗策略。 结果：传统化疗及靶向治疗（如酪氨酸激酶抑制剂）常因肿瘤微环境、基因突变及癌细胞异质性等因素而失效。休眠癌细胞可在静息状态下长期潜伏而不被察觉，一旦重新激活将导致显著的复发风险。这些细胞与内在耐药机制共同使治疗工作变得极为复杂。深入理解这些通路对于开发更有效的疗法至关重要。目前正在研究包括靶向多通路的联合疗法在内的新兴策略，以改善治疗结果。抗体药物偶联物和靶向蛋白降解等创新方法，通过将细胞毒性药物直接递送至癌细胞或降解癌细胞生存必需蛋白，提供了具有前景的解决方案。肺癌类器官模型在该领域展现出推动研究与临床应用的巨大潜力，有助于增强耐药机制研究和个体化治疗开发能力。现有研究的整合凸显了治疗模式持续创新的必要性。 结论：结合新型疗法与深入理解肿瘤生物学的个体化策略，对于克服肺癌中耐药及休眠癌细胞带来的挑战至关重要。多层面的综合治疗方法有望显著改善患者预后。
肿瘤(癌症)患者之家