Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition

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dc.contributor.authorHraběta, Jancs
dc.contributor.authorBelhajová, Mariecs
dc.contributor.authorŠubrtová, Hanacs
dc.contributor.authorMerlos Rodrigo, Miguel Ángelcs
dc.contributor.authorHeger, Zbyněkcs
dc.contributor.authorEckschlager, Tomášcs
dc.coverage.issue12cs
dc.coverage.volume21cs
dc.date.issued2020-06-30cs
dc.description.abstractResistance to chemotherapeutics and targeted drugs is one of the main problems in successful cancer therapy. Various mechanisms have been identified to contribute to drug resistance. One of those mechanisms is lysosome-mediated drug resistance. Lysosomes have been shown to trap certain hydrophobic weak base chemotherapeutics, as well as some tyrosine kinase inhibitors, thereby being sequestered away from their intracellular target site. Lysosomal sequestration is in most cases followed by the release of their content from the cell by exocytosis. Lysosomal accumulation of anticancer drugs is caused mainly by ion-trapping, but active transport of certain drugs into lysosomes was also described. Lysosomal low pH, which is necessary for ion-trapping is achieved by the activity of the V-ATPase. This sequestration can be successfully inhibited by lysosomotropic agents and V-ATPase inhibitors in experimental conditions. Clinical trials have been performed only with lysosomotropic drug chloroquine and their results were less successful. The aim of this review is to give an overview of lysosomal sequestration and expression of acidifying enzymes as yet not well known mechanism of cancer cell chemoresistance and about possibilities how to overcome this form of resistance.en
dc.formattextcs
dc.format.extent1-18cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationInternational Journal of Molecular Sciences. 2020, vol. 21, issue 12, p. 1-18.en
dc.identifier.doi10.3390/ijms21124392cs
dc.identifier.issn1422-0067cs
dc.identifier.orcid0000-0002-3915-7270cs
dc.identifier.other164789cs
dc.identifier.researcheridD-1973-2013cs
dc.identifier.urihttp://hdl.handle.net/11012/194873
dc.language.isoencs
dc.publisherMDPIcs
dc.relation.ispartofInternational Journal of Molecular Sciencescs
dc.relation.urihttps://www.mdpi.com/1422-0067/21/12/4392cs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1422-0067/cs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectchemoresistance of cancer cellsen
dc.subjectlysosomal sequestrationen
dc.subjectV-ATPaseen
dc.subjectmetallothioneinsen
dc.subjectlysosomotropic agentsen
dc.subjectV-ATPase inhibitorsen
dc.titleDrug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibitionen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-164789en
sync.item.dbtypeVAVen
sync.item.insts2025.02.03 15:49:59en
sync.item.modts2025.01.17 18:41:34en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
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