HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F24%3A00603745" target="_blank" >RIV/68081707:_____/24:00603745 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/24:00136690 RIV/00159816:_____/24:00081675 RIV/00209805:_____/24:00079855 RIV/00027162:_____/24:N0000114
Result on the web
<a href="https://www.nature.com/articles/s41416-024-02774-9#citeas" target="_blank" >https://www.nature.com/articles/s41416-024-02774-9#citeas</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41416-024-02774-9" target="_blank" >10.1038/s41416-024-02774-9</a>
Alternative languages
Result language
angličtina
Original language name
HIV-protease inhibitors potentiate the activity of carfilzomib in triple-negative breast cancer
Original language description
BackgroundResistance to chemotherapy is a major problem in the treatment of patients with triple-negative breast cancer (TNBC). Preclinical data suggest that TNBC is dependent on proteasomes, however, clinical observations indicate that the efficacy of proteasome inhibitors in TNBC may be limited, suggesting the need for combination therapies.MethodsWe compared bortezomib and carfilzomib and their combinations with nelfinavir and lopinavir in TNBC cell lines and primary cells with regard to their cytotoxic activity, functional proteasome inhibition, and induction of the unfolded protein response (UPR). Furthermore, we evaluated the involvement of sXBP1, ABCB1, and ABCG2 in the cytotoxic activity of drug combinations.ResultsCarfilzomib, via proteasome beta 5 + beta 2 inhibition, is more cytotoxic in TNBC than bortezomib, which inhibits beta 5 + beta 1 proteasome subunits. The cytotoxicity of carfilzomib was significantly potentiated by nelfinavir or lopinavir. Carfilzomib with lopinavir induced endoplasmic reticulum stress and pro-apoptotic UPR through the accumulation of excess proteasomal substrate protein in TNBC in vitro. Moreover, lopinavir increased the intracellular availability of carfilzomib by inhibiting carfilzomib export from cells that express high levels and activity of ABCB1, but not ABCG2.ConclusionProteasome inhibition by carfilzomib combined with nelfinavir/lopinavir represents a potential treatment option for TNBC, warranting further investigation.
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
30204 - Oncology
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
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
British Journal of Cancer
ISSN
0007-0920
e-ISSN
1532-1827
Volume of the periodical
5
Issue of the periodical within the volume
131
Country of publishing house
DE - GERMANY
Number of pages
13
Pages from-to
918-930
UT code for WoS article
001263310800001
EID of the result in the Scopus database
2-s2.0-85197486685