Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness

Comprising more than half of all brain tumors, glioblastoma multiforme (GBM) is a leading cause of brain cancer-related deaths worldwide. A major clinical challenge is presented by the capacity of glioma cells to rapidly infiltrate healthy brain parenchyma, allowing the cancer to escape control by l...

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Autores principales:	Alanah Varricchio, Sunita A. Ramesh, Andrea J. Yool
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glioma brain cancer glioblastoma aquaporin membrane intrinsic protein K<sub>V</sub> channel Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6d8b44e0f9b74d94a88d402e13b4e3de
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spelling	oai:doaj.org-article:6d8b44e0f9b74d94a88d402e13b4e3de2021-11-11T17:19:25ZNovel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness10.3390/ijms2221119091422-00671661-6596https://doaj.org/article/6d8b44e0f9b74d94a88d402e13b4e3de2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11909https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Comprising more than half of all brain tumors, glioblastoma multiforme (GBM) is a leading cause of brain cancer-related deaths worldwide. A major clinical challenge is presented by the capacity of glioma cells to rapidly infiltrate healthy brain parenchyma, allowing the cancer to escape control by localized surgical resections and radiotherapies, and promoting recurrence in other brain regions. We propose that therapies which target cellular motility pathways could be used to slow tumor dispersal, providing a longer time window for administration of frontline treatments needed to directly eradicate the primary tumors. An array of signal transduction pathways are known to be involved in controlling cellular motility. Aquaporins (AQPs) and voltage-gated ion channels are prime candidates as pharmacological targets to restrain cell migration in glioblastoma. Published work has demonstrated AQPs 1, 4 and 9, as well as voltage-gated potassium, sodium and calcium channels, chloride channels, and acid-sensing ion channels are expressed in GBM and can influence processes of cell volume change, extracellular matrix degradation, cytoskeletal reorganization, lamellipodial and filopodial extension, and turnover of cell-cell adhesions and focal assembly sites. The current gap in knowledge is the identification of optimal combinations of targets, inhibitory agents, and drug delivery systems that will allow effective intervention with minimal side effects in the complex environment of the brain, without disrupting finely tuned activities of neuro-glial networks. Based on published literature, we propose that co-treatments using AQP inhibitors in addition to other therapies could increase effectiveness, overcoming some limitations inherent in current strategies that are focused on single mechanisms. An emerging interest in nanobodies as drug delivery systems could be instrumental for achieving the selective delivery of combinations of agents aimed at multiple key targets, which could enhance success in vivo.Alanah VarricchioSunita A. RameshAndrea J. YoolMDPI AGarticlegliomabrain cancerglioblastomaaquaporinmembrane intrinsic proteinK<sub>V</sub> channelBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11909, p 11909 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioma brain cancer glioblastoma aquaporin membrane intrinsic protein K<sub>V</sub> channel Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	glioma brain cancer glioblastoma aquaporin membrane intrinsic protein K<sub>V</sub> channel Biology (General) QH301-705.5 Chemistry QD1-999 Alanah Varricchio Sunita A. Ramesh Andrea J. Yool Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness
description	Comprising more than half of all brain tumors, glioblastoma multiforme (GBM) is a leading cause of brain cancer-related deaths worldwide. A major clinical challenge is presented by the capacity of glioma cells to rapidly infiltrate healthy brain parenchyma, allowing the cancer to escape control by localized surgical resections and radiotherapies, and promoting recurrence in other brain regions. We propose that therapies which target cellular motility pathways could be used to slow tumor dispersal, providing a longer time window for administration of frontline treatments needed to directly eradicate the primary tumors. An array of signal transduction pathways are known to be involved in controlling cellular motility. Aquaporins (AQPs) and voltage-gated ion channels are prime candidates as pharmacological targets to restrain cell migration in glioblastoma. Published work has demonstrated AQPs 1, 4 and 9, as well as voltage-gated potassium, sodium and calcium channels, chloride channels, and acid-sensing ion channels are expressed in GBM and can influence processes of cell volume change, extracellular matrix degradation, cytoskeletal reorganization, lamellipodial and filopodial extension, and turnover of cell-cell adhesions and focal assembly sites. The current gap in knowledge is the identification of optimal combinations of targets, inhibitory agents, and drug delivery systems that will allow effective intervention with minimal side effects in the complex environment of the brain, without disrupting finely tuned activities of neuro-glial networks. Based on published literature, we propose that co-treatments using AQP inhibitors in addition to other therapies could increase effectiveness, overcoming some limitations inherent in current strategies that are focused on single mechanisms. An emerging interest in nanobodies as drug delivery systems could be instrumental for achieving the selective delivery of combinations of agents aimed at multiple key targets, which could enhance success in vivo.
format	article
author	Alanah Varricchio Sunita A. Ramesh Andrea J. Yool
author_facet	Alanah Varricchio Sunita A. Ramesh Andrea J. Yool
author_sort	Alanah Varricchio
title	Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness
title_short	Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness
title_full	Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness
title_fullStr	Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness
title_full_unstemmed	Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness
title_sort	novel ion channel targets and drug delivery tools for controlling glioblastoma cell invasiveness
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6d8b44e0f9b74d94a88d402e13b4e3de
work_keys_str_mv	AT alanahvarricchio novelionchanneltargetsanddrugdeliverytoolsforcontrollingglioblastomacellinvasiveness AT sunitaaramesh novelionchanneltargetsanddrugdeliverytoolsforcontrollingglioblastomacellinvasiveness AT andreajyool novelionchanneltargetsanddrugdeliverytoolsforcontrollingglioblastomacellinvasiveness
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Novel Ion Channel Targets and Drug Delivery Tools for Controlling Glioblastoma Cell Invasiveness

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