Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition.
Int J Mol Sci
; 21(12)2020 Jun 20.
Article
in English
| MEDLINE | ID: covidwho-742794
ABSTRACT
Resistance 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Drug Resistance, Neoplasm
/
Vacuolar Proton-Translocating ATPases
/
Lysosomes
/
Neoplasms
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Year:
2020
Document Type:
Article
Affiliation country:
Ijms21124392
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