FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3021066042> ?p ?o ?g. }

• W3021066042 abstract "Abstract Multiple myeloma is a plasma cell malignancy that escapes from apoptosis by heterogeneously over-expressing anti-apoptotic BCL2 proteins. Myeloma cells with a t(11;14) translocation present a particular vulnerability to BCL2 inhibition while a majority of myeloma cells relies on MCL1 for survival. The present study aimed to determine whether the combination of BCL2 and MCL1 inhibitors at low doses could be of benefit for myeloma cells beyond the single selective inhibition of BCL2 or MCL1. We identified that half of patients were not efficiently targeted neither by BCL2 inhibitor nor MCL1 inhibitor. Seventy percent of these myeloma samples, either from patients at diagnosis or relapse, presented a marked increase of apoptosis upon low dose combination of both inhibitors. Interestingly, primary cells from a patient in progression under venetoclax treatment were not sensitive ex vivo to neither venetoclax nor to MCL1 inhibitor, whereas the combination of both efficiently induced cell death. This finding suggests that the combination could overcome venetoclax resistance. The efficacy of the combination was also confirmed in U266 xenograft model resistant to BCL2 and MCL1 inhibitors. Mechanistically, we demonstrated that the combination of both inhibitors favors apoptosis in a BAX/BAK dependent manner. We showed that activated BAX was readily increased upon the inhibitor combination leading to the formation of BAK/BAX hetero-complexes. We found that BCLXL remains a major resistant factor of cell death induced by this combination. The present study supports a rational for the clinical use of venetoclax/S63845 combination in myeloma patients with the potential to elicit significant clinical activity when both single inhibitors would not be effective but also to overcome developed in vivo venetoclax resistance." @default.
• W3021066042 created "2020-05-13" @default.
• W3021066042 creator A5003041443 @default.
• W3021066042 creator A5003428531 @default.
• W3021066042 creator A5011827756 @default.
• W3021066042 creator A5021522769 @default.
• W3021066042 creator A5050667416 @default.
• W3021066042 creator A5051471778 @default.
• W3021066042 creator A5056464456 @default.
• W3021066042 creator A5066448346 @default.
• W3021066042 creator A5068580383 @default.
• W3021066042 creator A5076841614 @default.
• W3021066042 creator A5090948121 @default.
• W3021066042 date "2020-05-05" @default.
• W3021066042 modified "2023-10-14" @default.
• W3021066042 title "Dual targeting of BCL2 and MCL1 rescues myeloma cells resistant to BCL2 and MCL1 inhibitors associated with the formation of BAX/BAK hetero-complexes" @default.
• W3021066042 cites W1933867057 @default.
• W3021066042 cites W1965410156 @default.
• W3021066042 cites W1995770722 @default.
• W3021066042 cites W2020418292 @default.
• W3021066042 cites W2027482010 @default.
• W3021066042 cites W2050702798 @default.
• W3021066042 cites W2061425058 @default.
• W3021066042 cites W2110525250 @default.
• W3021066042 cites W2148404212 @default.
• W3021066042 cites W2172242534 @default.
• W3021066042 cites W2180824226 @default.
• W3021066042 cites W2485824342 @default.
• W3021066042 cites W2515091391 @default.
• W3021066042 cites W2534349779 @default.
• W3021066042 cites W2569998106 @default.
• W3021066042 cites W2761234508 @default.
• W3021066042 cites W2773012738 @default.
• W3021066042 cites W2794420547 @default.
• W3021066042 cites W2796392037 @default.
• W3021066042 cites W2889850618 @default.
• W3021066042 cites W2891173371 @default.
• W3021066042 cites W2892573863 @default.
• W3021066042 cites W2902472954 @default.
• W3021066042 cites W2904773508 @default.
• W3021066042 cites W2905070646 @default.
• W3021066042 cites W2906797443 @default.
• W3021066042 cites W2914157523 @default.
• W3021066042 cites W2916031169 @default.
• W3021066042 cites W2964193656 @default.
• W3021066042 cites W2991015399 @default.
• W3021066042 cites W2996593053 @default.
• W3021066042 cites W4294141750 @default.
• W3021066042 doi "https://doi.org/10.1038/s41419-020-2505-1" @default.
• W3021066042 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7200824" @default.
• W3021066042 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32371863" @default.
• W3021066042 hasPublicationYear "2020" @default.
• W3021066042 type Work @default.
• W3021066042 sameAs 3021066042 @default.
• W3021066042 citedByCount "29" @default.
• W3021066042 countsByYear W30210660422020 @default.
• W3021066042 countsByYear W30210660422021 @default.
• W3021066042 countsByYear W30210660422022 @default.
• W3021066042 countsByYear W30210660422023 @default.
• W3021066042 crossrefType "journal-article" @default.
• W3021066042 hasAuthorship W3021066042A5003041443 @default.
• W3021066042 hasAuthorship W3021066042A5003428531 @default.
• W3021066042 hasAuthorship W3021066042A5011827756 @default.
• W3021066042 hasAuthorship W3021066042A5021522769 @default.
• W3021066042 hasAuthorship W3021066042A5050667416 @default.
• W3021066042 hasAuthorship W3021066042A5051471778 @default.
• W3021066042 hasAuthorship W3021066042A5056464456 @default.
• W3021066042 hasAuthorship W3021066042A5066448346 @default.
• W3021066042 hasAuthorship W3021066042A5068580383 @default.
• W3021066042 hasAuthorship W3021066042A5076841614 @default.
• W3021066042 hasAuthorship W3021066042A5090948121 @default.
• W3021066042 hasBestOaLocation W30210660421 @default.
• W3021066042 hasConcept C104317684 @default.
• W3021066042 hasConcept C127561419 @default.
• W3021066042 hasConcept C185592680 @default.
• W3021066042 hasConcept C190283241 @default.
• W3021066042 hasConcept C203014093 @default.
• W3021066042 hasConcept C2776364478 @default.
• W3021066042 hasConcept C2776999253 @default.
• W3021066042 hasConcept C2777938653 @default.
• W3021066042 hasConcept C2778461978 @default.
• W3021066042 hasConcept C2779176958 @default.
• W3021066042 hasConcept C2779675984 @default.
• W3021066042 hasConcept C31573885 @default.
• W3021066042 hasConcept C502942594 @default.
• W3021066042 hasConcept C55493867 @default.
• W3021066042 hasConcept C71924100 @default.
• W3021066042 hasConcept C86803240 @default.
• W3021066042 hasConcept C98274493 @default.
• W3021066042 hasConceptScore W3021066042C104317684 @default.
• W3021066042 hasConceptScore W3021066042C127561419 @default.
• W3021066042 hasConceptScore W3021066042C185592680 @default.
• W3021066042 hasConceptScore W3021066042C190283241 @default.
• W3021066042 hasConceptScore W3021066042C203014093 @default.
• W3021066042 hasConceptScore W3021066042C2776364478 @default.
• W3021066042 hasConceptScore W3021066042C2776999253 @default.
• W3021066042 hasConceptScore W3021066042C2777938653 @default.
• W3021066042 hasConceptScore W3021066042C2778461978 @default.
• W3021066042 hasConceptScore W3021066042C2779176958 @default.
• W3021066042 hasConceptScore W3021066042C2779675984 @default.

• next