What Is the Significance of Lysosomal-Mediated Resistance to Imatinib?
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F23%3A73621711" target="_blank" >RIV/61989592:15110/23:73621711 - isvavai.cz</a>
Result on the web
<a href="https://www.mdpi.com/2073-4409/12/5/709" target="_blank" >https://www.mdpi.com/2073-4409/12/5/709</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cells12050709" target="_blank" >10.3390/cells12050709</a>
Alternative languages
Result language
angličtina
Original language name
What Is the Significance of Lysosomal-Mediated Resistance to Imatinib?
Original language description
The lysosomal sequestration of hydrophobic weak-base anticancer drugs is one proposed mechanism for the reduced availability of these drugs at target sites, resulting in a marked decrease in cytotoxicity and consequent resistance. While this subject is receiving increasing emphasis, it is so far only in laboratory experiments. Imatinib is a targeted anticancer drug used to treat chronic myeloid leukaemia (CML), gastrointestinal stromal tumours (GISTs), and a number of other malignancies. Its physicochemical properties make it a typical hydrophobic weak-base drug that accumulates in the lysosomes of tumour cells. Further laboratory studies suggest that this might significantly reduce its antitumor efficacy. However, a detailed analysis of published laboratory studies shows that lysosomal accumulation cannot be considered a clearly proven mechanism of resistance to imatinib. Second, more than 20 years of clinical experience with imatinib has revealed a number of resistance mechanisms, none of which is related to its accumulation in lysosomes. This review focuses on the analysis of salient evidence and raises a fundamental question about the significance of lysosomal sequestration of weak-base drugs in general as a possible resistance mechanism both in clinical and laboratory settings.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cells
ISSN
2073-4409
e-ISSN
2073-4409
Volume of the periodical
12
Issue of the periodical within the volume
5
Country of publishing house
CH - SWITZERLAND
Number of pages
15
Pages from-to
709
UT code for WoS article
000948067500001
EID of the result in the Scopus database
2-s2.0-85149778862