Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F23%3A73619587" target="_blank" >RIV/61989592:15310/23:73619587 - isvavai.cz</a>
Result on the web
<a href="https://link.springer.com/article/10.1007/s10637-023-01346-7" target="_blank" >https://link.springer.com/article/10.1007/s10637-023-01346-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s10637-023-01346-7" target="_blank" >10.1007/s10637-023-01346-7</a>
Alternative languages
Result language
angličtina
Original language name
Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines
Original language description
Small molecule Bruton’s tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitor for anticancer therapy in 2013. Previous reports proved the receptor kinase human epidermal growth factor receptor 2 (HER2) to be a valid off-target kinase of ibrutinib and potentially other irreversible BTK inhibitors, as it possesses a druggable cysteine residue in the active site of the enzyme. These findings suggest ibrutinib as a candidate drug for repositioning in HER2-positive breast cancer (BCa). This subtype of breast cancer belongs to one of the most common classes of breast tumours, and its prognosis is characterized by a high rate of recurrence and tumour invasiveness. Based on their similar kinase selectivity profiles, we investigated the anticancer effect of zanubrutinib, evobrutinib, tirabrutinib and acalabrutinib in different BCa cell lines and sought to determine whether it is linked with targeting the epidermal growth factor receptor family (ERBB) pathway. We found that zanubrutinib is a potential inhibitor of the HER2 signalling pathway, displaying an antiproliferative effect in HER2-positive BCa cell lines. Zanubrutinib effectively inhibits the phosphorylation of proteins in the ERBB signalling cascade, including the downstream kinases Akt and ERK, which mediate key signals ensuring the survival and proliferation of cancer cells. We thus propose zanubrutinib as another suitable candidate for repurposing in HER2-amplified solid tumours.
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
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
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
INVESTIGATIONAL NEW DRUGS
ISSN
0167-6997
e-ISSN
1573-0646
Volume of the periodical
41
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
210-219
UT code for WoS article
000948384500001
EID of the result in the Scopus database
2-s2.0-85149894515