Tirabrutinib-anthracycline interactions in the brain tumor microenvironment: a focus on metabolic inactivation and resistance
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10509886" target="_blank" >RIV/00216208:11160/25:10509886 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=_g7jsL2m0r" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=_g7jsL2m0r</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1080/17425255.2025.2595661" target="_blank" >10.1080/17425255.2025.2595661</a>
Alternative languages
Result language
angličtina
Original language name
Tirabrutinib-anthracycline interactions in the brain tumor microenvironment: a focus on metabolic inactivation and resistance
Original language description
Background: Anthracyclines (ANTs) remain essential in many anticancer regimens, yet their clinical utility is often limited by multidrug resistance. Recent studies suggest that Bruton's tyrosine kinase inhibitors (BTKis) may enhance the efficacy of ANT-based therapies, including those targeting brain tumors. This study investigates how tirabrutinib may contribute to such enhancement via interactions with aldo-keto reductase 1C3 (AKR1C3) and ABC efflux transporters. Research design and methods: The inhibitory potential of tirabrutinib was evaluated using recombinant enzymes, transiently transfected HCT116 cells, and cell lines with differential AKR1C3 expression (T98G, MRC-5). ABC transporter-expressing cells were used to assess daunorubicin accumulation. Western blotting was used to examine whether tirabrutinib alters AKR1C3 protein expression. Results:Tirabrutinib inhibited daunorubicin metabolism in both recombinant AKR1C3 assays and AKR1C3-expressing cells, but had no effect in non-expressing cells. It also enhanced intracellular accumulation of daunorubicin in relevant models. No significant changes in AKR1C3 expression were observed following tirabrutinib treatment. Conclusions: Our in vitro data demonstrate that tirabrutinib influences daunorubicin pharmacodynamics by targeting both metabolic and transport pathways. However, Chou-Talalay analysis highlights the importance of appropriate dosing to achieve therapeutic synergy in combination regimens.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
<a href="/en/project/EH22_008%2F0004607" target="_blank" >EH22_008/0004607: New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Expert Opinion on Drug Metabolism & Toxicology
ISSN
1742-5255
e-ISSN
1744-7607
Volume of the periodical
21
Issue of the periodical within the volume
11-12
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
1315-1326
UT code for WoS article
001629080100001
EID of the result in the Scopus database
2-s2.0-105023706658