As distinct cancer biomarkers have been discovered in recent years, a need to reclassify tumors by more than their histology has been proposed, and therapies are now tailored to treat cancers based on specific molecular aberrations and immunologic markers. In fact, multiple histology-agnostic therapies are currently adopted in clinical practice for treating patients regardless of their tumor site of origin. In parallel with this new model for drug development, in the past few years, several novel antibody–drug conjugates (ADCs) have been approved to treat solid tumors, benefiting from engineering improvements in the conjugation process and the introduction of novel linkers and payloads. With the recognition that numerous surface targets are expressed across various cancer histologies, alongside the remarkable activity of modern ADCs, this drug class has been increasingly evaluated as suitable for a histology-agnostic expansion of indication. For illustration, the anti-HER2 ADC trastuzumab deruxtecan has demonstrated compelling activity in HER2-overexpressing breast, gastric, colorectal, and lung cancer. Examples of additional novel and potentially histology-agnostic ADC targets include trophoblast cell-surface antigen 2 (Trop-2) and nectin-4, among others. In the current review article, the authors summarize the current approvals of ADCs by the US Food and Drug Administration focusing on solid tumors and discuss the challenges and opportunities posed by the multihistological expansion of ADCs.

中文翻译：

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抗体-药物偶联物：跨肿瘤组织学的智能化疗递送

由于近年来发现了不同的癌症生物标志物，因此提出了对肿瘤进行重新分类的需求，而不仅仅是组织学，并且现在根据特定的分子畸变和免疫学标志物来定制治疗癌症的疗法。事实上，目前在临床实践中采用多种与组织学无关的疗法来治疗患者，无论其肿瘤起源于何处。与这种新的药物开发模式同时，在过去几年中，一些新型抗体-药物偶联物 (ADC) 已被批准用于治疗实体瘤，这得益于偶联过程的工程改进以及新型接头和有效载荷的引入。认识到在各种癌症组织学中表达了许多表面靶标，以及现代 ADC 的显着活性，这种药物类别已越来越多地被评估为适用于与组织学无关的适应症扩展。例如，抗 HER2 ADC 曲妥珠单抗 deruxtecan 在 HER2 过度表达的乳腺癌、胃癌、结直肠癌和肺癌中显示出令人信服的活性。其他新的和可能与组织学无关的 ADC 靶标的例子包括滋养层细胞表面抗原 2 (Trop-2) 和 nectin-4 等。在当前的评论文章中，作者总结了美国食品和药物管理局目前对实体瘤的批准，并讨论了 ADC 的多组织学扩展带来的挑战和机遇。抗 HER2 ADC 曲妥珠单抗 deruxtecan 在 HER2 过表达的乳腺癌、胃癌、结直肠癌和肺癌中显示出令人信服的活性。其他新的和可能与组织学无关的 ADC 靶标的例子包括滋养层细胞表面抗原 2 (Trop-2) 和 nectin-4 等。在当前的评论文章中，作者总结了美国食品和药物管理局目前对实体瘤的批准，并讨论了 ADC 的多组织学扩展带来的挑战和机遇。抗 HER2 ADC 曲妥珠单抗 deruxtecan 在 HER2 过表达的乳腺癌、胃癌、结直肠癌和肺癌中显示出令人信服的活性。其他新的和可能与组织学无关的 ADC 靶标的例子包括滋养层细胞表面抗原 2 (Trop-2) 和 nectin-4 等。在当前的评论文章中，作者总结了美国食品和药物管理局目前批准的针对实体瘤的 ADC，并讨论了 ADC 的多组织学扩展带来的挑战和机遇。