Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials.
Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials.
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DOI：
10.3389/fonc.2022.959630
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发表时间：
2022
影响因子：
4.7
通讯作者：
Moore, Anna
中科院分区：
文献类型：
--
作者：
Savan, N. Anna;Saavedra, Paulo Vilar;Halim, Alan;Yuzbasiyan-Gurkan, Vilma;Wang, Ping;Yoo, Byunghee;Kiupel, Matti;Sempere, Lorenzo;Medarova, Zdravka;Moore, Anna
90%的癌症死亡是由转移引起的。MiRNAs在增殖、转移、凋亡和自我更新等生物学过程中起着关键作用。我们和其他人之前已经证明了miRNA-10b促进转移细胞的迁移和侵袭。重要的是，我们还表明miR-10b是转移细胞存活和增殖的关键驱动因素。为了通过抑制miR-10b来治疗已建立的转移，我们使用了一种名为MN-anti-miR10b的治疗性药物，它由抗miR-10b反义寡核糖体组成，与氧化铁纳米颗粒结合，作为体内肿瘤细胞的载体和磁共振成像(MRI)报告。在我们之前使用小鼠转移性乳腺癌模型的研究中，我们证明了MN-抗miR10b在预防和消除现有转移方面的有效性。为了展望我们的治疗方法的临床翻译，我们在这里报告了对患有自发性猫科动物乳腺癌(FMC)的大型动物(伴猫)的研究。我们首先研究了miR-10b在猫肿瘤和转移瘤中的表达和组织定位，并显示出与人类这些特征的显著相似之处。接下来，在涉及这种治疗的第一个病例研究中，我们给一名FMC患者静脉注射了MN-抗miR10b，并使用MRI证明了它对转移灶的输送。我们还展示了该疗法的初步安全性概况，并显示在给药后miR-10b表达及其靶点HOXD10发生了显著变化。我们的结果为利用伴侣动物进一步开发MN-抗miR10b作为一种治疗方法提供了支持，并为未来在人类患者身上进行临床试验提供了指导。
Ninety percent of deaths from cancer are caused by metastasis. miRNAs are critical players in biological processes such as proliferation, metastasis, apoptosis, and self-renewal. We and others have previously demonstrated that miRNA-10b promotes metastatic cell migration and invasion. Importantly, we also showed that miR-10b is a critical driver of metastatic cell viability and proliferation. To treat established metastases by inhibiting miR-10b, we utilized a therapeutic, termed MN-anti-miR10b, composed of anti-miR-10b antagomirs, conjugated to iron oxide nanoparticles, that serve as delivery vehicles to tumor cells in vivo and a magnetic resonance imaging (MRI) reporter. In our previous studies using murine models of metastatic breast cancer, we demonstrated the effectiveness of MN-anti-miR10b in preventing and eliminating existing metastases. With an outlook toward clinical translation of our therapeutic, here we report studies in large animals (companion cats) with spontaneous feline mammary carcinoma (FMC). We first investigated the expression and tissue localization of miR-10b in feline tumors and metastases and showed remarkable similarity to these features in humans. Next, in the first case study involving this therapeutic we intravenously dosed an FMC patient with MN-anti-miR10b and demonstrated its delivery to the metastatic lesions using MRI. We also showed the initial safety profile of the therapeutic and demonstrated significant change in miR-10b expression and its target HOXD10 after dosing. Our results provide support for using companion animals for further MN-anti-miR10b development as a therapy and serve as a guide for future clinical trials in human patients.
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影响因子：
46.9
作者：
Ma L;Reinhardt F;Pan E;Soutschek J;Bhat B;Marcusson EG;Teruya-Feldstein J;Bell GW;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
8.8
作者：
James, JJ;Evans, AJ;Robertson, JFR
通讯作者：
Robertson, JFR
影响因子：
1.3
作者：
Biller, Barb;Berg, John;Bryan, Christine
通讯作者：
Bryan, Christine
DOI：
10.1007/s10555-021-09995-x
发表时间：
2021-09
期刊：
Cancer metastasis reviews
影响因子：
--
作者：
Sempere LF;Powell K;Rana J;Brock AA;Schmittgen TD
通讯作者：
Schmittgen TD
影响因子：
2.8
作者：
Min W;Wang B;Li J;Han J;Zhao Y;Su W;Dai Z;Wang X;Ma Q
通讯作者：
Ma Q