文章：

开启小细胞肺癌治疗新纪元：抗体药物偶联物的崛起

Unlocking New Horizons in Small-Cell Lung Cancer Treatment: The Onset of Antibody–Drug Conjugates

原文发布日期：10 November 2023

DOI: 10.3390/cancers15225368

类型: Article

开放获取: 是

英文摘要：

Small-cell lung cancer (SCLC) is a highly aggressive disease, accounting for about 15% of all lung cancer cases. Despite initial responses to chemoimmunotherapy, SCLC recurs and becomes resistant to treatment. Recently, antibody–drug conjugates (ADCs) have emerged as a promising therapeutic option for SCLC. ADCs consist of an antibody that specifically targets a tumor antigen linked to a cytotoxic drug. The antibody delivers the drug directly to the cancer cells, minimizing off-target toxicity and improving the therapeutic index. Several ADCs targeting different tumor antigens are currently being evaluated in clinical trials for SCLC. Despite the negative results of rovalpituzumab tesirine (Rova-T), other ADCs targeting different antigens, such as B7-H3, seizure-related homolog 6 (SEZ6), and CEACAM5, have also been investigated in clinical trials, including for SCLC, and their results suggest preliminary activity, either alone or in combination with other therapies. More recently, sacituzumab govitecan, an anti-TROP2 ADC, demonstrated promising activity in lung cancer, including SCLC. Furthermore, an anti-B7-H3 (CD276), ifinatamab deruxtecan (DS7300A), showed a high response rate and durable responses in heavily pretreated SCLC. Overall, ADCs represent an intriguing approach to treating SCLC, particularly in the relapsed or refractory setting. Further studies are needed to determine their efficacy and safety and the best location in the treatment algorithm for SCLC. In this review, we aim to collect and describe the results regarding the past, the present, and the future of ADCs in SCLC.

摘要翻译： 

小细胞肺癌（SCLC）是一种高度侵袭性的疾病，约占所有肺癌病例的15%。尽管初始对化疗免疫疗法有反应，但SCLC会复发并对治疗产生耐药性。近年来，抗体药物偶联物（ADCs）已成为SCLC的一种有前景的治疗选择。ADCs由特异性靶向肿瘤抗原的抗体与细胞毒性药物连接而成。抗体将药物直接递送至癌细胞，最大限度地减少脱靶毒性并提高治疗指数。目前，针对不同肿瘤抗原的多种ADCs正在SCLC的临床试验中进行评估。尽管rovalpituzumab tesirine（Rova-T）取得了阴性结果，但针对其他抗原（如B7-H3、癫痫相关同源蛋白6（SEZ6）和CEACAM5）的ADCs也在包括SCLC在内的临床试验中进行了研究，其结果显示单独或联合其他疗法具有初步活性。最近，抗TROP2 ADC sacituzumab govitecan在包括SCLC在内的肺癌中显示出有前景的活性。此外，抗B7-H3（CD276）药物ifinatamab deruxtecan（DS7300A）在经重度预处理的SCLC中表现出高应答率和持久应答。总体而言，ADCs代表了一种治疗SCLC的有趣方法，特别是在复发或难治性情况下。需要进一步研究以确定其疗效和安全性，以及在SCLC治疗算法中的最佳定位。在本综述中，我们旨在收集并描述ADCs在SCLC的过去、现在和未来的相关结果。

原文链接：

Unlocking New Horizons in Small-Cell Lung Cancer Treatment: The Onset of Antibody–Drug Conjugates