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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...

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Autores principales: Savan, N. Anna, Saavedra, Paulo Vilar, Halim, Alan, Yuzbasiyan-Gurkan, Vilma, Wang, Ping, Yoo, Byunghee, Kiupel, Matti, Sempere, Lorenzo, Medarova, Zdravka, Moore, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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