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Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials
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, w...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643803/ https://www.ncbi.nlm.nih.gov/pubmed/36387245 http://dx.doi.org/10.3389/fonc.2022.959630 |
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author | Savan, N. Anna Saavedra, Paulo Vilar Halim, Alan Yuzbasiyan-Gurkan, Vilma Wang, Ping Yoo, Byunghee Kiupel, Matti Sempere, Lorenzo Medarova, Zdravka Moore, Anna |
author_facet | Savan, N. Anna Saavedra, Paulo Vilar Halim, Alan Yuzbasiyan-Gurkan, Vilma Wang, Ping Yoo, Byunghee Kiupel, Matti Sempere, Lorenzo Medarova, Zdravka Moore, Anna |
author_sort | Savan, N. Anna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9643803 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96438032022-11-15 Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials Savan, N. Anna Saavedra, Paulo Vilar Halim, Alan Yuzbasiyan-Gurkan, Vilma Wang, Ping Yoo, Byunghee Kiupel, Matti Sempere, Lorenzo Medarova, Zdravka Moore, Anna Front Oncol Oncology 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. Frontiers Media S.A. 2022-10-26 /pmc/articles/PMC9643803/ /pubmed/36387245 http://dx.doi.org/10.3389/fonc.2022.959630 Text en Copyright © 2022 Savan, Saavedra, Halim, Yuzbasiyan-Gurkan, Wang, Yoo, Kiupel, Sempere, Medarova and Moore https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Savan, N. Anna Saavedra, Paulo Vilar Halim, Alan Yuzbasiyan-Gurkan, Vilma Wang, Ping Yoo, Byunghee Kiupel, Matti Sempere, Lorenzo Medarova, Zdravka Moore, Anna Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
title | Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
title_full | Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
title_fullStr | Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
title_full_unstemmed | Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
title_short | Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
title_sort | case report: microrna-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643803/ https://www.ncbi.nlm.nih.gov/pubmed/36387245 http://dx.doi.org/10.3389/fonc.2022.959630 |
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