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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 ...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
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.
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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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