The Journey of Antibody-Drug Conjugates: Lessons Learned from 40 Years of Development.

IF 29.7 1区 医学 Q1 ONCOLOGY
Raffaele Colombo,Paolo Tarantino,Jamie R Rich,Patricia M LoRusso,Elisabeth G E de Vries
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Abstract

Antibody-drug conjugates (ADC) represent one of the most rapidly expanding treatment modalities in oncology, with 11 ADCs approved by the FDA and more than 210 currently being tested in clinical trials. Spanning over 40 years, ADC clinical development has enhanced our understanding of the multifaceted mechanisms of action for this class of therapeutics. In this article, we discuss key insights into the toxicity, efficacy, stability, distribution, and fate of ADCs. Furthermore, we highlight ongoing challenges related to their clinical optimization, the development of rational sequencing strategies, and the identification of predictive biomarkers. Significance: The development and utilization of ADCs have allowed for relevant improvements in the prognosis of multiple cancer types. Concomitantly, the rise of ADCs in oncology has produced several challenges, including the prediction of their activity, their utilization in sequence, and minimization of their side effects, that still too often resemble those of the cytotoxic molecule that they carry. In this review, we retrace 40 years of development in the field of ADCs and delve deep into the mechanisms of action of these complex therapeutics and reasons behind the many achievements and failures observed in the field to date.
抗体药物共轭物的发展历程:从 40 年的发展中汲取的经验教训。
抗体药物共轭物(ADC)是肿瘤学领域发展最迅速的治疗方式之一,目前已有 11 种 ADC 获得美国食品及药物管理局(FDA)批准,210 多种 ADC 正在接受临床试验。ADC 临床开发历时 40 余年,加深了我们对该类疗法多方面作用机制的了解。在本文中,我们将讨论有关 ADC 的毒性、疗效、稳定性、分布和转归的重要见解。此外,我们还重点介绍了在临床优化、合理测序策略的开发以及预测性生物标记物的鉴定方面所面临的挑战。意义重大:ADCs 的开发和利用使多种癌症类型的预后得到了相关改善。与此同时,ADCs 在肿瘤学领域的兴起也带来了一些挑战,包括对其活性的预测、按顺序使用以及最大限度地减少其副作用,而这些副作用往往与它们所携带的细胞毒性分子的副作用相似。在这篇综述中,我们回顾了 ADC 领域 40 年的发展历程,并深入探讨了这些复杂疗法的作用机制,以及该领域迄今为止取得的众多成就和失败背后的原因。
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来源期刊
Cancer discovery
Cancer discovery ONCOLOGY-
CiteScore
22.90
自引率
1.40%
发文量
838
审稿时长
6-12 weeks
期刊介绍: Cancer Discovery publishes high-impact, peer-reviewed articles detailing significant advances in both research and clinical trials. Serving as a premier cancer information resource, the journal also features Review Articles, Perspectives, Commentaries, News stories, and Research Watch summaries to keep readers abreast of the latest findings in the field. Covering a wide range of topics, from laboratory research to clinical trials and epidemiologic studies, Cancer Discovery spans the entire spectrum of cancer research and medicine.
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