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Blocking channels to metastasis: targeting sodium transport in breast cancer

The development of therapies that can suppress invasion and prevent metastasis, ‘anti-metastatic drugs’, is an important area of unmet therapeutic need. The new results of a recent open-label, multicentre randomised trial published in J Clin Oncol showed a significant disease-free survival (DFS) ben...

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Autores principales: Brackenbury, William J., Palmieri, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638823/
https://www.ncbi.nlm.nih.gov/pubmed/37950273
http://dx.doi.org/10.1186/s13058-023-01741-1
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author Brackenbury, William J.
Palmieri, Carlo
author_facet Brackenbury, William J.
Palmieri, Carlo
author_sort Brackenbury, William J.
collection PubMed
description The development of therapies that can suppress invasion and prevent metastasis, ‘anti-metastatic drugs’, is an important area of unmet therapeutic need. The new results of a recent open-label, multicentre randomised trial published in J Clin Oncol showed a significant disease-free survival (DFS) benefit for breast cancer patients receiving presurgical, peritumoral injection of lidocaine, an amide local anaesthetic, which blocks voltage-gated sodium channels (VGSCs). VGSCs are expressed on electrically excitable cells, including neurons and cardiomyocytes, where they sustain rapid membrane depolarisation during action potential firing. As a result of this key biophysical function, VGSCs are important drug targets for excitability-related disorders, including epilepsy, neuropathic pain, affective disorders and cardiac arrhythmia. A growing body of preclinical evidence highlights VGSCs as key protagonists in regulating altered sodium influx in breast cancer cells, thus driving invasion and metastasis. Furthermore, prescription of certain VGSC-inhibiting medications has been associated with reduced cancer incidence and improved survival in several observational studies. Thus, VGSC-inhibiting drugs already in clinical use may be ideal candidates for repurposing as possible anti-metastatic therapies. While these results are promising, further work is required to establish whether other VGSC inhibitors may afford superior metastasis suppression. Finally, increasing preclinical evidence suggests that several other ion channels are also key drivers of cancer hallmarks; thus, there are undoubtedly further opportunities to harness ion transport inhibition that should also be explored.
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spelling pubmed-106388232023-11-11 Blocking channels to metastasis: targeting sodium transport in breast cancer Brackenbury, William J. Palmieri, Carlo Breast Cancer Res Perspective The development of therapies that can suppress invasion and prevent metastasis, ‘anti-metastatic drugs’, is an important area of unmet therapeutic need. The new results of a recent open-label, multicentre randomised trial published in J Clin Oncol showed a significant disease-free survival (DFS) benefit for breast cancer patients receiving presurgical, peritumoral injection of lidocaine, an amide local anaesthetic, which blocks voltage-gated sodium channels (VGSCs). VGSCs are expressed on electrically excitable cells, including neurons and cardiomyocytes, where they sustain rapid membrane depolarisation during action potential firing. As a result of this key biophysical function, VGSCs are important drug targets for excitability-related disorders, including epilepsy, neuropathic pain, affective disorders and cardiac arrhythmia. A growing body of preclinical evidence highlights VGSCs as key protagonists in regulating altered sodium influx in breast cancer cells, thus driving invasion and metastasis. Furthermore, prescription of certain VGSC-inhibiting medications has been associated with reduced cancer incidence and improved survival in several observational studies. Thus, VGSC-inhibiting drugs already in clinical use may be ideal candidates for repurposing as possible anti-metastatic therapies. While these results are promising, further work is required to establish whether other VGSC inhibitors may afford superior metastasis suppression. Finally, increasing preclinical evidence suggests that several other ion channels are also key drivers of cancer hallmarks; thus, there are undoubtedly further opportunities to harness ion transport inhibition that should also be explored. BioMed Central 2023-11-10 2023 /pmc/articles/PMC10638823/ /pubmed/37950273 http://dx.doi.org/10.1186/s13058-023-01741-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 Perspective
Brackenbury, William J.
Palmieri, Carlo
Blocking channels to metastasis: targeting sodium transport in breast cancer
title Blocking channels to metastasis: targeting sodium transport in breast cancer
title_full Blocking channels to metastasis: targeting sodium transport in breast cancer
title_fullStr Blocking channels to metastasis: targeting sodium transport in breast cancer
title_full_unstemmed Blocking channels to metastasis: targeting sodium transport in breast cancer
title_short Blocking channels to metastasis: targeting sodium transport in breast cancer
title_sort blocking channels to metastasis: targeting sodium transport in breast cancer
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638823/
https://www.ncbi.nlm.nih.gov/pubmed/37950273
http://dx.doi.org/10.1186/s13058-023-01741-1
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