With 9.6 million deaths in 2018, cancer represents one of the most common causes of death, both in men and women. Despite recent advances in the understanding of molecular mechanisms involved in cancer development and progression, treatment options are still limited. Limitations of traditional chemotherapy include the lack of selectivity and the unfavorable safety profile. The efficacy of targeted therapies (e.g., tyrosine kinase inhibitors) is also limited by their cytostatic action, which inhibits tumor cell proliferation without inducing tumor cell death, and by the risk of acquired resistance. Antibody-drug conjugates (ADCs), a newly developed class of engineered anticancer drugs, consist of recombinant monoclonal antibodies against tumor-specific antigens that are covalently bound to cytotoxic agents. They have been designed to overcome the limitations of traditional chemotherapy and targeted therapies by combining the target selectivity of monoclonal antibodies with the high potency of cytotoxic drugs. Currently, ADCs that have received regulatory approval include brentuximab vedotin for CD30-positive Hodgkin lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2-positive breast cancer. However, over 80 novel ADCs are actively being investigated in preclinical studies and early-phase clinical trials. In this review, we will provide a comprehensive overview of the biological rational, efficacy and safety of ADCs as therapeutic agents against non-small cell lung cancer and small cell lung cancer.

中文翻译：

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个体化肿瘤学时代肺癌的抗体-药物偶联物。

2018 年有 960 万人死亡，癌症是男性和女性最常见的死因之一。尽管最近在对参与癌症发展和进展的分子机制的理解方面取得了进展，但治疗选择仍然有限。传统化疗的局限性包括缺乏选择性和不利的安全性。靶向治疗（例如酪氨酸激酶抑制剂）的功效还受到其抑制肿瘤细胞增殖而不诱导肿瘤细胞死亡的细胞抑制作用以及获得性耐药风险的限制。抗体-药物偶联物 (ADC) 是一类新开发的工程抗癌药物，由与细胞毒剂共价结合的针对肿瘤特异性抗原的重组单克隆抗体组成。它们旨在通过将单克隆抗体的靶向选择性与细胞毒性药物的高效力相结合来克服传统化学疗法和靶向疗法的局限性。目前，已获得监管批准的 ADC 包括用于 CD30 阳性霍奇金淋巴瘤的 brentuximab vedotin 和用于人表皮生长因子受体 2 阳性乳腺癌的曲妥珠单抗 emtansine。然而，临床前研究和早期临床试验正在积极研究 80 多种新型 ADC。在这篇综述中，我们将全面概述 ADC 作为非小细胞肺癌和小细胞肺癌治疗药物的生物学合理性、有效性和安全性。