-
EP4 receptor agonist L-902688 augments cytotoxic activities of ibrutinib, idelalisib, and venetoclax against chronic lymphocytic leukemia cellsNabergoj, Sanja ...Treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) has significantly improved more recently with the approval of several new agents, including ibrutinib, idelalisib, ... and venetoclax. Despite the outstanding efficacies observed with these agents, these treatments are sometimes discontinued due to toxicity, unresponsiveness, transformation of the disease and/or resistance. Constitutive NF-[kappa]B activation that protects CLL cells from apoptotic stimuli represents one of molecular mechanisms that underlie the emergence of drug resistance. As prostaglandin E (EP)4 receptor agonists have been shown to successfully inhibit the NF-[kappa]B pathway in B-cell lymphoma cells, we investigated the potential of the highly specific EP4 receptor agonist L-902688 for the potential treatment of patients with CLL. We show here that low micromolar concentrations of L-902688 can indeed induce selective cytotoxicity towards several B-cell malignancies, including CLL. Moreover, L-902688-mediated activation of the EP4 receptor in patient derived CLL cells resulted in inhibition of the NF-[kappa]B pathway, cell proliferation, and induction of apoptosis. Most importantly, we show for the first time that in combination with ibrutinib, idelalisib, or venetoclax, L-902688 induces synergistic cytotoxic activity against patient derived CLL cells. To conclude, the modulation of NF-[kappa]B activity by EP4 receptor agonists represents an innovative approach to improve the treatment of patients with CLL. In particular, EP4 receptor agonists appear to represent promising adjuncts to the already existing therapies for patients with CLL due to these promising synergistic activities.Source: Biochemical pharmacology. - ISSN 0006-2952 (Vol. 183, 2021, str. 1-14)Type of material - article, component part ; adult, seriousPublish date - 2021Language - englishCOBISS.SI-ID - 43415299
Author
Nabergoj, Sanja |
Markovič, Tijana |
Avsec, Damjan, farmacevt, 1993- |
Gobec, Martina, 1983- |
Podgornik, Helena |
Jakopin, Žiga |
Mlinarič-Raščan, Irena
Topics
Kronična limfocitna levkemija |
Citotoksičnost |
chronic lymphocytic leukemia |
L-902688 |
NF-{kappa]B inhibition |
prostaglandin E4 |
receptor |
synergistic cytotoxic activity |
prostaglandin E4 |
receptorji |
sinergistična citotoksična aktivnost |
celice kronične limfocitne levkemije
Author | Nabergoj, Sanja ... |
Title | EP4 receptor agonist L-902688 augments cytotoxic activities of ibrutinib, idelalisib, and venetoclax against chronic lymphocytic leukemia cells |
Publication date | 2021-01-29 |
COBISS.SI-ID | 43415299 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution-NoDerivatives 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
---|---|---|---|
NOBIL - Novi biološki označevalci v levkemiji | NC-0004-2018 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin | P1-0208-2015 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
Files that belong to the publication
Link |
---|
https://www.sciencedirect.com/science/article/pii/S0006295220305888#! |
https://repozitorij.uni-lj.si/IzpisGradiva.php?id=138397 |
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|---|
Nabergoj, Sanja | 38165 |
Markovič, Tijana | 34223 |
Avsec, Damjan, farmacevt, 1993- | 52092 |
Gobec, Martina, 1983- | 32034 |
Podgornik, Helena | 12684 |
Jakopin, Žiga | 26496 |
Mlinarič-Raščan, Irena | 12443 |
Select pickup location:
Material pickup by post
Notification
Subject headings in COBISS General List of Subject Headings
Select pickup location
Pickup location | Material status | Reservation |
---|
Please wait a moment.