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| 驱动基因阴性非小细胞肺癌一线免疫化疗后治疗的研究进展 |
| Research Progress on First-Line Immunotherapy and Chemotherapy for Non-Small Cell Lung Cancer with Negative Driver Genes |
| 投稿时间：2025-05-20 修订日期：2025-08-07 |
| DOI： |
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| 中文关键词: 驱动基因阴性 NSCLC 二线治疗 临床研究 |
| 英文关键词:driver negative NSCLC second-line treatment clinical study |
| 基金项目:国家自然科学基金项目课题(编号82473392) ,国家自然科学基金项目（面上项目，重点项目，重大项目） |
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| 中文摘要: |
| 对于驱动基因阴性晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者,当前一线治疗方案主要包括PD-1/L1抑制剂联合化疗、抗血管生成药物联合化疗以及免疫单药治疗。其中,基于免疫联合化疗的方案已显著改善患者生存结局,然而临床实践中仍面临原发性/获得性耐药及疾病进展的挑战。目前,一线化疗联合免疫治疗失败后的耐药机制可分为三大类：肿瘤细胞内在调控机制、肿瘤微环境动态重塑及宿主系统因素。当前研究耐药机制热点集中在以下治疗策略：抗体药物偶联物(ADC)、双免疫检查点抑制剂联合治疗方案,以及靶向耐药通路的新型治疗探索。本文围绕肿瘤免疫微环境重塑、表观遗传调控等耐药机制,综述新型治疗策略及未来研究方向。 |
| 英文摘要: |
| For patients with advanced non-small cell lung cancer (NSCLC) with negative driver genes, the current first-line treatment options mainly include PD-1/L1 inhibitors combined with chemotherapy, anti-angiogenic drugs combined with chemotherapy, and single-agent immunotherapy. Among them, the combination of immunotherapy and chemotherapy has significantly improved the survival outcomes of patients. However, in clinical practice, challenges such as primary/acquired resistance and disease progression still exist. Currently, the resistance mechanisms after the failure of first-line chemotherapy combined with immunotherapy can be classified into three major categories: intrinsic regulatory mechanisms of tumor cells, dynamic remodeling of the tumor microenvironment, and host system factors. The current research hotspots on resistance mechanisms focus on the following treatment strategies: antibody-drug conjugates (ADCs), combination therapy with dual immune checkpoint inhibitors, and exploration of novel treatments targeting resistance pathways. This article reviews the novel treatment strategies and future research directions centered on the remodeling of the tumor immune microenvironment and epigenetic regulation, among other resistance mechanisms. |
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