| 石文惠,李子明.抗体药物偶联物：晚期非小细胞肺癌治疗新策略[J].肿瘤学杂志,2025,31(7):578-585. |
| 抗体药物偶联物：晚期非小细胞肺癌治疗新策略 |
| Antibody-Drug Conjugate： New Strategy for the Treatment of Advanced Non-Small Cell Lung Cancer |
| 投稿时间：2024-11-29 |
| DOI：10.11735/j.issn.1671-170X.2025.07.B003 |
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| 中文关键词: 抗体药物偶联物 非小细胞肺癌 治疗策略 |
| 英文关键词:antibody-drug conjugate non-small cell lung cancer treatment strategy |
| 基金项目:上海申康医院发展中心第二轮《促进市级医院临床技能与临床创新三年行动计划》研究型医师创新转化能力培训项目 （SHDC2023CRD022） |
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| 中文摘要: |
| 摘 要：抗体药物偶联物（antibody-drug conjugate，ADC）作为新型精准抗肿瘤药物，为非小细胞肺癌（non-small cell lung carcer，NSCLC）的治疗提供了新的治疗选择。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作用。目前，靶向人表皮生长因子受体2、人表皮生长因子受体3、靶向滋养层细胞表面抗原2、表皮生长因子受体和间质表皮转化因子的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策略，以进一步提高疗效并降低不良反应。全文综述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。 |
| 英文摘要: |
| Abstract： Antibody-drug conjugate(ADC) represent an innovative class of targeted anticancer agents that have introduced new therapeutic possibilities for non-small cell lung cancer(NSCLC). The fundamental architecture of ADC incorporates three essential elements： a highly specific monoclonal antibody， a selectively cleavable linker， and a potent cytotoxic payload. 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 ADC directed against various molecular targets， including human epidermal growth factor receptor 2， human epidermal growth factor receptor 3，trophoblast cell surface antigen 2， epidermal growth factor receptor，and celluar-mesenchymal epithelial transition factor. 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 techniques， novel target identification， and strategic combination regimens to enhance treatment outcomes and safety profiles. While ADC 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. This paper 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. |
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