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揭示抗体药物偶联物在治疗三阴性乳腺癌中的应用:治疗趋势与未来展望。

Unveiling the antibody-drug conjugates portfolio in battling Triple-negative breast cancer: Therapeutic trends and Future horizon.

机构信息

Department of Pharmacology, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, 380009, India.

Consultant Medical Oncologist, ClearMedi Radiant Hospital, Mysore, 570017, India.

出版信息

Med Oncol. 2022 Dec 2;40(1):25. doi: 10.1007/s12032-022-01884-9.

Abstract

Triple-negative breast cancer (TNBC) showcases a labyrinthine network exhibiting deficient expression of Estrogen receptor (ER), Progesterone receptor (PR), and Human-epidermal growth factor receptor-2 (HER2). This restricts the conventional chemotherapeutic, hormonal, and few targeted regimens in showing efficient anti-tumor response. Antibody-drug conjugates (ADCs) are target-specific conjugates comprising a monoclonal antibody attached to the desired cytotoxic payload with the support of a stable linker. They are designated as one of the encouraging sets of targeted therapies that have unveiled affirmative outcomes owing to increased specificity in targeting the undetectable or deficiently expressed targets. Another virtue of ADCs lending superiority to this approach is the presence of inherent bystander effect which has a detrimental influence on the tumor microenvironment (TME) devoid of antigen expression. In the current scenario, FDA-approved Sacituzumab govitecan is widely being utilized to mitigate TNBC while many other ADCs are being studied in clinical trials. Additionally, a focus has been set on revelation of application of Trastuzumab deruxtecan in HER2-low metastatic breast cancer which widens the current therapeutic horizon dealing with such carcinomas. After making an effort towards sketching ADCs profile, we conclude that this novel approach deserves to be investigated through future campaigns owing to its remarkable bystander effect, ability to precisely recognize the antigen and spare the naïve cells from detrimental toxicity. Exploration of the remarkable potential of Sacituzumab govitecan in multiple indications including TNBC portrays the prominence of ADCs and prompts the bright future of this therapeutic approach. In this review, we present the basic foundation of ADCs alongside summarizing the building blocks of several ADCs used in TNBC. Furthermore, by shedding light on the therapeutic regimens and concomitant effects of various ADCs derived from the supportive backbone of clinical trials, we have attempted to convene several segments of ADCs and portray their potentialities time ahead.

摘要

三阴性乳腺癌(TNBC)表现出一种错综复杂的网络,其雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体 2(HER2)表达不足。这限制了传统的化疗、激素和少数靶向方案的有效抗肿瘤反应。抗体药物偶联物(ADC)是一种靶向特异性偶联物,由与所需细胞毒性有效载荷连接的单克隆抗体和稳定的连接子组成。它们被指定为一类有希望的靶向治疗药物之一,由于增加了针对不可检测或表达不足的靶标的特异性,因此取得了积极的结果。ADC 具有内在旁观者效应,对缺乏抗原表达的肿瘤微环境(TME)产生不利影响,这是它们优于其他方法的另一个优点。在当前情况下,FDA 批准的Sacituzumab govitecan 广泛用于治疗 TNBC,而许多其他 ADC 正在临床试验中进行研究。此外,人们还关注 Trastuzumab deruxtecan 在 HER2 低转移性乳腺癌中的应用,这拓宽了目前治疗此类癌症的治疗范围。在努力描绘 ADC 概况之后,我们得出结论,由于其显著的旁观者效应、精确识别抗原的能力以及使幼稚细胞免受有害毒性的能力,这种新方法值得通过未来的研究进行探索。在多种适应症中探索 Sacituzumab govitecan 的显著潜力,包括 TNBC,突显了 ADC 的重要性,并预示着这种治疗方法的光明未来。在这篇综述中,我们介绍了 ADC 的基本原理,并总结了用于 TNBC 的几种 ADC 的构建模块。此外,通过阐明来自临床试验支持性骨干的各种 ADC 的治疗方案和伴随效应,我们试图汇集 ADC 的几个部分,并描绘它们未来的潜力。

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