Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody–drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy tissues. This study aims to explore the effectiveness and challenges associated with ADCs in NSCLC, with a focus on drug-induced interstitial lung disease (D-ILD). Methods: A comprehensive literature review was conducted across MEDLINE (Ovid), Embase (Elsevier), CENTRAL (Cochrane Library), and other sources up to March 2023, to identify ADCs used in NSCLC treatment and their associated risk of D-ILD. The incidence of ILD was analyzed from clinical trial data, while ADC target expression was examined through RNA and protein levels in normal and tumor lung tissues. Discussion: Our findings highlight the therapeutic potential of ADCs in NSCLC, as evidenced by significant clinical outcomes. However, the occurrence of D-ILD presents a notable challenge, as its incidence was not directly correlated with the expression levels of the target antigens. This suggests that D-ILD may result from factors beyond antigen expression, including the cytotoxic payload and linker characteristics of ADCs. Conclusion: ADCs offer a promising avenue for NSCLC treatment. Nonetheless, the risk of D-ILD necessitates a balanced approach in ADC development, focusing on optimizing linker and payload properties to mitigate this adverse effect. Further research is essential to better understand and manage D-ILD, ensuring the safe and effective use of ADCs in clinical practice.
引言：尽管免疫检查点抑制剂和靶向治疗取得进展，非小细胞肺癌（NSCLC）仍是全球癌症相关死亡的主要原因。抗体药物偶联物（ADCs）通过特异性向癌细胞递送细胞毒性药物，有望减少对健康组织的损害，代表了一种前景广阔的治疗策略。本研究旨在探讨ADCs在NSCLC治疗中的有效性及挑战，重点关注药物相关性间质性肺病（D-ILD）。方法：通过系统检索截至2023年3月的MEDLINE（Ovid）、Embase（Elsevier）、CENTRAL（Cochrane图书馆）等数据库，全面梳理用于NSCLC治疗的ADCs及其相关D-ILD风险。基于临床试验数据分析ILD发生率，并通过正常肺组织与肿瘤组织的RNA及蛋白水平检测ADC靶点表达情况。讨论：研究结果证实ADCs在NSCLC治疗中具有显著临床疗效，展现出重要治疗潜力。然而D-ILD的发生构成突出挑战，其发生率与靶抗原表达水平无直接相关性，提示D-ILD可能源于抗原表达之外的多重因素，包括ADC的细胞毒性载荷及连接子特性。结论：ADCs为NSCLC治疗提供了新方向，但D-ILD风险要求我们在ADC研发中采取平衡策略，通过优化连接子与载荷特性来降低此类不良反应。未来需深入开展研究以深化对D-ILD的认知与管理，确保ADCs在临床实践中的安全有效应用。
肿瘤(癌症)患者之家