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Microtubule disruption reduces metastasis more effectively than primary tumor growth
Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 ...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842877/ https://www.ncbi.nlm.nih.gov/pubmed/35164808 http://dx.doi.org/10.1186/s13058-022-01506-2 |
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author | Thompson, Keyata N. Ju, Julia A. Ory, Eleanor C. Pratt, Stephen J. P. Lee, Rachel M. Mathias, Trevor J. Chang, Katarina T. Lee, Cornell J. Goloubeva, Olga G. Bailey, Patrick C. Chakrabarti, Kristi R. Jewell, Christopher M. Vitolo, Michele I. Martin, Stuart S. |
author_facet | Thompson, Keyata N. Ju, Julia A. Ory, Eleanor C. Pratt, Stephen J. P. Lee, Rachel M. Mathias, Trevor J. Chang, Katarina T. Lee, Cornell J. Goloubeva, Olga G. Bailey, Patrick C. Chakrabarti, Kristi R. Jewell, Christopher M. Vitolo, Michele I. Martin, Stuart S. |
author_sort | Thompson, Keyata N. |
collection | PubMed |
description | Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01506-2. |
format | Online Article Text |
id | pubmed-8842877 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88428772022-02-16 Microtubule disruption reduces metastasis more effectively than primary tumor growth Thompson, Keyata N. Ju, Julia A. Ory, Eleanor C. Pratt, Stephen J. P. Lee, Rachel M. Mathias, Trevor J. Chang, Katarina T. Lee, Cornell J. Goloubeva, Olga G. Bailey, Patrick C. Chakrabarti, Kristi R. Jewell, Christopher M. Vitolo, Michele I. Martin, Stuart S. Breast Cancer Res Research Article Clinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-022-01506-2. BioMed Central 2022-02-14 2022 /pmc/articles/PMC8842877/ /pubmed/35164808 http://dx.doi.org/10.1186/s13058-022-01506-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Thompson, Keyata N. Ju, Julia A. Ory, Eleanor C. Pratt, Stephen J. P. Lee, Rachel M. Mathias, Trevor J. Chang, Katarina T. Lee, Cornell J. Goloubeva, Olga G. Bailey, Patrick C. Chakrabarti, Kristi R. Jewell, Christopher M. Vitolo, Michele I. Martin, Stuart S. Microtubule disruption reduces metastasis more effectively than primary tumor growth |
title | Microtubule disruption reduces metastasis more effectively than primary tumor growth |
title_full | Microtubule disruption reduces metastasis more effectively than primary tumor growth |
title_fullStr | Microtubule disruption reduces metastasis more effectively than primary tumor growth |
title_full_unstemmed | Microtubule disruption reduces metastasis more effectively than primary tumor growth |
title_short | Microtubule disruption reduces metastasis more effectively than primary tumor growth |
title_sort | microtubule disruption reduces metastasis more effectively than primary tumor growth |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842877/ https://www.ncbi.nlm.nih.gov/pubmed/35164808 http://dx.doi.org/10.1186/s13058-022-01506-2 |
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