抗体药物偶联物（ADC）是现代药物开发中增长最快的肿瘤学药物之一。通过利用细胞毒性化疗和靶向治疗的作用，ADC在为表达某种预定义细胞表面靶标的癌细胞提供高效能的细胞毒素药物方面具有独特的优势。在肺癌领域，近年来治疗范式发生了巨大变化，ADC现在已成为肺癌患者的潜在治疗选择之一。自2020年以来，第一种ADC用于NSCLC患者已获得美国FDA批准（曲妥珠单抗-德伍汀），另外两种ADC已被授予FDA突破性疗法认定，并正在接受评估（巴曲妥珠单抗-德伍汀，特利索妥珠单抗-韦杜汀）。此外，还有几项早期试验正在评估多种新型ADC，既可以作为单一治疗，也可以与晚期肺癌联合治疗，并有望成为临床中的治疗选择。在本综述中，我们将讨论ADC的结构和作用机制，包括来自临床前工作的洞见，总结ADC在肺癌方面的最新进展，描述ADC的毒性剖面，并探索旨在增强ADC效力并克服耐药性的策略。此外，我们还将讨论肺癌领域感兴趣的新型ADC策略，包括非细胞毒性荷载，如免疫调节剂和抗凋亡剂。 © 2023年书稿作者。

Antibody-drug conjugates (ADCs) are one of fastest growing classes of oncology drugs in modern drug development. By harnessing the powers of both cytotoxic chemotherapy and targeted therapy, ADCs are unique in offering the potential to deliver highly potent cytotoxic agents to cancer cells which express a pre-defined cell surface target. In lung cancer, the treatment paradigm has shifted dramatically in recent years, and now ADCs are now joining the list as potential options for lung cancer patients. Since 2020, the first ADC for NSCLC patients has been FDA-approved (trastuzumab deruxtecan) and two ADCs have been granted FDA Breakthrough Therapy Designation, currently under evaluation (patritumab deruxtecan, telisotuzumab vedotin). Furthermore, several early-phase trials are assessing various novel ADCs, either as monotherapy or in combinations with advanced lung cancer, and more selective and potent ADCs are expected to become therapeutic options in clinic soon. In this review, we discuss the structure and mechanism of action of ADCs, including insights from pre-clinical work; we summarize the ADCs' recent progress in lung cancer, describe toxicity profiles of ADCs, and explore strategies designed to enhance ADC potency and overcome resistance. In addition, we discuss novel ADC strategies of interest in lung cancer, including non-cytotoxic payloads, such as immunomodulatory and anti-apoptotic agents.© 2023. The Author(s).