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靶向 Trop-2 在癌症中的研究进展及临床应用。

Targeting Trop-2 in cancer: Recent research progress and clinical application.

机构信息

Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China; Laboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.

Department of Medical Oncology, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, China.

出版信息

Biochim Biophys Acta Rev Cancer. 2023 Jul;1878(4):188902. doi: 10.1016/j.bbcan.2023.188902. Epub 2023 Apr 29.

Abstract

The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy. Up to now, the mechanisms and functions associated with Trop-2 have been extensively studied in a variety of solid tumors. According to these findings, Trop-2 plays an important role in cell proliferation, apoptosis, cell adhesion, epithelial-mesenchymal transition, as well as tumorigenesis and tumor progression. In addition, Trop-2 related drugs are also being developed widely. There are a number of Trop-2 related ADC drugs that have demonstrated potent antitumor activity and are currently been studied, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd). In this study, we reviewed the progress of Trop-2 research in solid tumors. We also sorted out the composition and rationale of Trop-2 related drugs and summarized the related clinical trials. Finally, we discussed the current status of Trop-2 research and expanded our perspectives on its future research directions. Importantly, we found that Trop-2 targeted ADCs have great potential for combination with other antitumor therapies. Trop-2 targeted ADCs can reprogramme tumor microenvironment through multiple signaling pathways, ultimately activating antitumor immunity.

摘要

新型抗肿瘤药物的开发主要依赖于对肿瘤细胞的精准靶向。滋养层表面抗原 2(Trop-2)是一种Ⅰ型跨膜糖蛋白,参与肿瘤细胞中的 Ca 信号转导。它在各种肿瘤组织中的表达高于正常组织,是癌症靶向治疗的一个新颖而有前途的分子靶点。到目前为止,Trop-2 的相关机制和功能已在多种实体瘤中得到广泛研究。根据这些发现,Trop-2 在细胞增殖、凋亡、细胞黏附、上皮间质转化以及肿瘤发生和肿瘤进展中发挥着重要作用。此外,Trop-2 相关药物也在广泛开发中。有许多 Trop-2 相关的 ADC 药物已被证明具有强大的抗肿瘤活性,并正在进行研究,例如 Sacituzumab Govitecan(SG)和 Datopotamab Deruxtecan(Dato-Dxd)。在本研究中,我们回顾了 Trop-2 在实体瘤中的研究进展。我们还梳理了 Trop-2 相关药物的组成和原理,并总结了相关的临床试验。最后,我们讨论了 Trop-2 研究的现状,并扩展了对其未来研究方向的看法。重要的是,我们发现 Trop-2 靶向 ADC 与其他抗肿瘤疗法联合具有巨大的潜力。Trop-2 靶向 ADC 可通过多种信号通路重新编程肿瘤微环境,最终激活抗肿瘤免疫。

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