Satti Siem A, Sheikh M Saeed
Department of Pharmacology, Sate University of New York, Upstate Medical University, Syracuse, New York.
New York Institute of Technology, Old Westbury, New York.
Mol Cell Pharmacol. 2023;15(1):1-5.
Sacituzumab govitecan is an antibody-drug conjugate. It is composed of a humanized monoclonal antibody raised against the trophoblast cell-surface antigen 2 (Trop-2), and linked to SN-38, which is an active metabolite of topoisomerase I inhibitor anticancer drug irinotecan. A hydrolyzable linker conjugates the antibody and the drug. Trop-2 is overexpressed in various tumors including the triple-negative breast cancers (TNBCs) that are more aggressive with limited therapeutic options. Sacituzumab govitecan has proven to be an important therapeutic modality to manage the TNBCs. It has shown progression-free survival (PFS) and overall survival (OS) benefits when compared to standard-of-care chemotherapeutics. Accordingly, it is approved for the treatment of TNBCs in the United States and the European Union. Sacituzumab govitecan has also shown PFS and OS benefits for hormone receptor-positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancers. Therefore, sacituzumab govitecan appears to be an option for HR+/HER2- metastatic breast cancers that are heavily pretreated and exhibit endocrine resistance. Although sacituzumab govitecan has shown promise, it also is toxic. Additional studies are therefore needed to further refine the use of sacituzumab govitecan in improving the management of metastatic breast cancer.
戈沙妥珠单抗是一种抗体药物偶联物。它由一种针对滋养层细胞表面抗原2(Trop-2)产生的人源化单克隆抗体组成,并与SN-38连接,SN-38是拓扑异构酶I抑制剂抗癌药物伊立替康的活性代谢产物。一种可水解的连接子将抗体和药物偶联在一起。Trop-2在包括三阴性乳腺癌(TNBC)在内的各种肿瘤中过度表达,这些肿瘤侵袭性更强且治疗选择有限。戈沙妥珠单抗已被证明是治疗TNBC的一种重要治疗方式。与标准护理化疗药物相比,它已显示出无进展生存期(PFS)和总生存期(OS)获益。因此,它在美国和欧盟被批准用于治疗TNBC。戈沙妥珠单抗在激素受体阳性(HR+)和人表皮生长因子受体2阴性(HER2-)转移性乳腺癌中也显示出PFS和OS获益。因此,戈沙妥珠单抗似乎是HR+/HER2-转移性乳腺癌的一种选择,这些患者经过大量预处理且表现出内分泌抵抗。尽管戈沙妥珠单抗已显示出前景,但它也有毒性。因此,需要进一步的研究来进一步优化戈沙妥珠单抗在改善转移性乳腺癌管理中的应用。