Trastuzumab is a fully humanized monoclonal antibody directed at HER2 which binds the external domain of the receptor and exerts its action via a combination of antibody-dependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation[1,2]. Trastuzumab is used as a standard treatment for breast and metastatic gastric cancer when the cancer cells overexpress HER2[3].
Trastuzumab combined with MZ1 significantly decreased cell proliferation, the formation of three-dimensional structures and cellular invasion compared to either of the drugs alone[4]. Trastuzumab treated HER2-overexpressing breast cancer cell lines results in induction of p27KIP1 and the Rb-related protein, p130, which in turn significantly reduces the number of cells undergoing S-phase. A number of other phenotypic changes are observed in vitro as a consequence of trastuzumab binding to HER2-overexpressing cells[5]. Trastuzumab-dendrimer-fluorine drug delivery system is a new form of trastuzumab to treat breast cancer cells in vitro. The potential of Trastuzumab-dendrimer-fluorine drug delivery system is more efficient than trastuzumab alone[6]
Trastuzumab causes a significant growth inhibition of the outgrowth of macroscopic JIMT-1 xenograft tumors in both nude and SCID mice[7]. The administration of MZ1 and trastuzumab induced a reduction in tumor progression, while individual treatments failed to do so[4]
References:
[1]. Ning G, Zhu Q, et al. A novel treatment strategy for lapatinib resistance in a subset of HER2-amplified gastric cancer. BMC Cancer. 2021;21(1):923. Published 2021 Aug 16. doi:10.1186/s12885-021-08283-9
[2]. Okines AF, Cunningham D. Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer. Therap Adv Gastroenterol. 2012 Sep;5(5):301-18.
[3]. Sarosiek T, Morawski P. Trastuzumab and its biosimilars [Trastuzumab and its biosimilars]. Pol Merkur Lekarski. 2018 May 25;44(263):253-257. Polish.
[4]. Noblejas-López MDM, Nieto-Jiménez C, et al. MZ1 co-operates with trastuzumab in HER2 positive breast cancer. J Exp Clin Cancer Res. 2021 Mar 19;40(1):106.
[5]. Sliwkowski MX, Lofgren JA, et al. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999 Aug;26(4 Suppl 12):60-70.
[6]. Bartusik-Aebisher D, Chrzanowski G, et al. An analytical study of Trastuzumab-dendrimer-fluorine drug delivery system in breast cancer therapy in vitro. Biomed Pharmacother. 2021 Jan;133:111053.
[7]. Barok M, Isola J, et al. Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance. Mol Cancer Ther. 2007 Jul;6(7):2065-72.
曲妥珠单抗是一种针对 HER2 的完全人源化单克隆抗体，它结合受体的外部结构域，并通过抗体依赖性细胞毒性、减少细胞外结构域脱落、抑制二聚化和可能的受体下调来发挥作用[1,2]。当癌细胞过度表达 HER2[3] 时，曲妥珠单抗被用作乳腺癌和转移性胃癌的标准治疗方法。
与单独使用任何一种药物相比，曲妥珠单抗联合 MZ1 可显着降低细胞增殖、三维结构的形成和细胞侵袭[4]。曲妥珠单抗处理的 HER2 过表达乳腺癌细胞系导致 p27KIP1 和 Rb 相关蛋白 p130 的诱导，这反过来显着减少了经历 S 期的细胞数量。由于曲妥珠单抗与 HER2 过表达细胞结合，在体外观察到许多其他表型变化[5]。曲妥珠单抗-树枝状大分子-氟药物递送系统是一种新形式的曲妥珠单抗，可在体外治疗乳腺癌细胞。曲妥珠单抗-树枝状大分子-氟药物递送系统的潜力比单独使用曲妥珠单抗更有效[6]
曲妥珠单抗可显着抑制裸鼠和 SCID 小鼠肉眼可见的 JIMT-1 异种移植肿瘤的生长[7]。 MZ1 和曲妥珠单抗的给药诱导了肿瘤进展的减缓，而单独的治疗则未能做到这一点[4]