The clinical development and then the progressive entry in clinical practice of antibody-drug conjugates (ADCs) have marked a transformative advancement in the overall cancer treatment. ADCs have been extensively tested for a large number of tumors, reporting heterogeneous clinical efficacy and safety results. In some diseases, the advent of ADCs has yielded significant changes in the prognostic trajectory, portending an improvement of the survival and/or quality of life. ADCs are targeted agents, capable of delivering highly cytotoxic payloads selectively to antigen-expressing cancer cells. As such, they have been intended as perfect ‘bullets’ to enable the promise of precision medicine, toward high-efficacy and limited-toxicity treatment options. However, only some approved ADCs are intended for the use in biomarker-selected patient populations, restricting potentially the opportunity to be more precise. Yet, key characteristics of modern ADCs might allow the activity of ADCs in tumors with heterogeneous or low expression of cancer antigens, resulting in a clinical activity that could sublimate the classic paradigm of a drug-to-target perfect match. In our review, we portrayed the current landscape of approved ADCs, reporting data of activity as related to the expression of the cancer antigens, and elucidating possible determinants of the safety and efficacy, including when used in a therapeutic sequence.

中文翻译：

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实体瘤中抗体-药物偶联物的生物标志物

抗体药物偶联物（ADC）的临床发展以及随后逐步进入临床实践标志着整个癌症治疗的变革性进步。ADC 已针对大量肿瘤进行了广泛测试，报告了不同的临床疗效和安全性结果。在某些疾病中，ADC 的出现使预后轨迹发生了显着变化，预示着生存率和/或生活质量的改善。ADC 是靶向药物，能够选择性地将高细胞毒性有效负载递送至表达抗原的癌细胞。因此，它们被视为完美的“子弹”，以实现精准医学的承诺，实现高效且毒性有限的治疗选择。然而，只有一些批准的 ADC 旨在用于生物标志物选择的患者群体，这可能限制了更精确的机会。然而，现代 ADC 的关键特征可能允许 ADC 在癌症抗原异质或低表达的肿瘤中发挥活性，从而产生一种可以升华药物与靶标完美匹配的经典范例的临床活性。在我们的综述中，我们描述了已批准 ADC 的现状，报告了与癌症抗原表达相关的活性数据，并阐明了安全性和有效性的可能决定因素，包括在治疗序列中使用时的情况。