|
| 抗体偶联药物：晚期非小细胞肺癌治疗新策略 |
| Antibody-conjugated Drugs : a New Strategy for the Treatment of Advanced Non-small Cell Lung Cancer |
| 投稿时间：2024-11-29 修订日期：2025-06-30 |
| DOI： |
|
 |
| 中文关键词: 抗体偶联药物 肺癌 非小细胞肺癌 单克隆抗体 |
| 英文关键词:antibody drug conjugates,lung cancer,NSCLC,monoclonal antibody |
| 基金项目: |
|
| 摘要点击次数: 0 |
| 全文下载次数: 0 |
| 中文摘要: |
| 抗体-药物偶联物（ADC）作为新型精准抗肿瘤药物，为非小细胞肺癌（NSCLC）的治疗提供了新的治疗选择。本文综述了ADC的作用机制、靶点选择及临床研究进展，并探讨其面临的挑战与未来发展方向。ADC由单克隆抗体、可裂解连接子和强效细胞毒性药物组成，通过特异性结合肿瘤表面抗原并内化释放载荷，实现高效低毒的肿瘤杀伤。目前，靶向 HER2（如T-DXd）、TROP-2（如Dato-DXd）、EGFR（如BL-B01D1）、c-MET（如Teliso-V）、Her3（HER3-DXd） 的ADC在临床试验中展现出显著疗效，然而，ADC仍存在靶抗原异质性、耐药性及脱靶毒性等问题，未来研究应聚焦于优化药物设计，如双特异性ADC、新型连接子技术、并继续探索新靶点及联合治疗治疗策略，以进一步提高疗效并降低不良反应。尽管ADC在NSCLC治疗中已取得重要突破，其安全性、药物耐药问题仍需继续探索。 |
| 英文摘要: |
| Antibody-drug conjugates (ADCs) represent an innovative class of targeted anticancer agents that have introduced new therapeutic possibilities for non-small cell lung carcinoma(NSCLC). This article provides a comprehensive analysis of ADC mechanisms, target selection criteria, and clinical trial outcomes, while critically examining existing limitations and potential advancements in the field. The fundamental architecture of ADCs incorporates three essential elements: a highly specific monoclonal antibody, a selectively cleavable linker, and a potent cytotoxic agent. These components work synergistically to achieve selective tumor targeting through antigen recognition, efficient cellular internalization, and controlled payload release, thereby maximizing therapeutic effects while minimizing systemic toxicity. Recent clinical investigations have highlighted the substantial antitumor activity of ADCs directed against various molecular targets, including HER2(e.g. trastuzumab deruxtecan), TROP-2(e.g. datopotamab deruxtecan), EGFR(e.g. BL-B01D1), c-MET (e.g. telisotuzumab vedotin), and HER3(e.g. patritumab deruxtecan). Nevertheless, several significant challenges persist, most notably tumor target heterogeneity, acquired drug resistance mechanisms, and therapy-related toxicities. Future developmental efforts should prioritize structural optimization approaches, encompassing bispecific antibody engineering, advanced linker technologies, novel target identification, and strategic combination regimens to enhance treatment outcomes and safety profiles. While ADCs have demonstrated clinically meaningful benefits in NSCLC management, further research is imperative to fully elucidate their long-term safety characteristics and overcome resistance development. Continued investigation into these areas will be crucial for realizing the complete therapeutic potential of this promising drug class. |
|
在线阅读
查看/发表评论 下载PDF阅读器 |
|
|
|