Matches in SemOpenAlex for { <https://semopenalex.org/work/W4280599358> ?p ?o ?g. }
Showing items 1 to 95 of
95
with 100 items per page.
- W4280599358 abstract "Triple negative breast cancer (TNBC) accounts for over 30% of all breast cancer-related deaths, despite accounting for only 10% to 15% of total breast cancer cases. Targeted therapy development has largely stalled in TNBC, underlined by a lack of traditionally druggable addictions like receptor tyrosine kinases (RTKs). Here, through full genome CRISPR/Cas9 screening of TNBC models, we have uncovered the sensitivity of TNBCs to the depletion of the Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1). Targeting UBA1 with the first in-class UBA1 inhibitor TAK-243 induced unresolvable ER-stress and activating transcription factor 4 (ATF4)-mediated upregulation of pro-apoptotic NOXA, leading to cell death. In five patient derived xenograft models (PDXs) of TNBC, TAK-243 therapy led to tumor inhibition or frank tumor regression. In an intracardiac metastatic model of TNBC, TAK-243 markedly reduced metastatic burden. Importantly, there was an order of magnitude greater sensitivity of TNBC lines to TAK-243 compared to normal tissue-derived cells. Lastly, c-MYC expression correlates with TAK-243 sensitivity and cooperates with TAK-243 to induce a stress response and cell death. We posit UBA1 is an important new target in TNBC expressing high levels of c-MYC." @default.
- W4280599358 created "2022-05-22" @default.
- W4280599358 creator A5005863962 @default.
- W4280599358 creator A5014545659 @default.
- W4280599358 creator A5015077321 @default.
- W4280599358 creator A5018148392 @default.
- W4280599358 creator A5019364289 @default.
- W4280599358 creator A5020741942 @default.
- W4280599358 creator A5031312383 @default.
- W4280599358 creator A5040148157 @default.
- W4280599358 creator A5047855938 @default.
- W4280599358 creator A5049700214 @default.
- W4280599358 creator A5050946845 @default.
- W4280599358 creator A5051463796 @default.
- W4280599358 creator A5054248424 @default.
- W4280599358 creator A5056470952 @default.
- W4280599358 creator A5057868655 @default.
- W4280599358 creator A5060699951 @default.
- W4280599358 creator A5065885586 @default.
- W4280599358 creator A5071844087 @default.
- W4280599358 creator A5089402878 @default.
- W4280599358 creator A5090051930 @default.
- W4280599358 date "2022-05-19" @default.
- W4280599358 modified "2023-10-16" @default.
- W4280599358 title "Genomic screening reveals UBA1 as a potent and druggable target in c-MYC-high TNBC models" @default.
- W4280599358 doi "https://doi.org/10.1101/2022.05.17.491908" @default.
- W4280599358 hasPublicationYear "2022" @default.
- W4280599358 type Work @default.
- W4280599358 citedByCount "0" @default.
- W4280599358 crossrefType "posted-content" @default.
- W4280599358 hasAuthorship W4280599358A5005863962 @default.
- W4280599358 hasAuthorship W4280599358A5014545659 @default.
- W4280599358 hasAuthorship W4280599358A5015077321 @default.
- W4280599358 hasAuthorship W4280599358A5018148392 @default.
- W4280599358 hasAuthorship W4280599358A5019364289 @default.
- W4280599358 hasAuthorship W4280599358A5020741942 @default.
- W4280599358 hasAuthorship W4280599358A5031312383 @default.
- W4280599358 hasAuthorship W4280599358A5040148157 @default.
- W4280599358 hasAuthorship W4280599358A5047855938 @default.
- W4280599358 hasAuthorship W4280599358A5049700214 @default.
- W4280599358 hasAuthorship W4280599358A5050946845 @default.
- W4280599358 hasAuthorship W4280599358A5051463796 @default.
- W4280599358 hasAuthorship W4280599358A5054248424 @default.
- W4280599358 hasAuthorship W4280599358A5056470952 @default.
- W4280599358 hasAuthorship W4280599358A5057868655 @default.
- W4280599358 hasAuthorship W4280599358A5060699951 @default.
- W4280599358 hasAuthorship W4280599358A5065885586 @default.
- W4280599358 hasAuthorship W4280599358A5071844087 @default.
- W4280599358 hasAuthorship W4280599358A5089402878 @default.
- W4280599358 hasAuthorship W4280599358A5090051930 @default.
- W4280599358 hasBestOaLocation W42805993581 @default.
- W4280599358 hasConcept C101544691 @default.
- W4280599358 hasConcept C104317684 @default.
- W4280599358 hasConcept C10679952 @default.
- W4280599358 hasConcept C121608353 @default.
- W4280599358 hasConcept C184235292 @default.
- W4280599358 hasConcept C2780110267 @default.
- W4280599358 hasConcept C2781230642 @default.
- W4280599358 hasConcept C502942594 @default.
- W4280599358 hasConcept C530470458 @default.
- W4280599358 hasConcept C54355233 @default.
- W4280599358 hasConcept C71924100 @default.
- W4280599358 hasConcept C86339819 @default.
- W4280599358 hasConcept C86803240 @default.
- W4280599358 hasConcept C98108389 @default.
- W4280599358 hasConceptScore W4280599358C101544691 @default.
- W4280599358 hasConceptScore W4280599358C104317684 @default.
- W4280599358 hasConceptScore W4280599358C10679952 @default.
- W4280599358 hasConceptScore W4280599358C121608353 @default.
- W4280599358 hasConceptScore W4280599358C184235292 @default.
- W4280599358 hasConceptScore W4280599358C2780110267 @default.
- W4280599358 hasConceptScore W4280599358C2781230642 @default.
- W4280599358 hasConceptScore W4280599358C502942594 @default.
- W4280599358 hasConceptScore W4280599358C530470458 @default.
- W4280599358 hasConceptScore W4280599358C54355233 @default.
- W4280599358 hasConceptScore W4280599358C71924100 @default.
- W4280599358 hasConceptScore W4280599358C86339819 @default.
- W4280599358 hasConceptScore W4280599358C86803240 @default.
- W4280599358 hasConceptScore W4280599358C98108389 @default.
- W4280599358 hasLocation W42805993581 @default.
- W4280599358 hasOpenAccess W4280599358 @default.
- W4280599358 hasPrimaryLocation W42805993581 @default.
- W4280599358 hasRelatedWork W1966181922 @default.
- W4280599358 hasRelatedWork W2366029130 @default.
- W4280599358 hasRelatedWork W2397277945 @default.
- W4280599358 hasRelatedWork W2551769070 @default.
- W4280599358 hasRelatedWork W2902027030 @default.
- W4280599358 hasRelatedWork W3007675372 @default.
- W4280599358 hasRelatedWork W3160512888 @default.
- W4280599358 hasRelatedWork W4289865969 @default.
- W4280599358 hasRelatedWork W4304606871 @default.
- W4280599358 hasRelatedWork W4323521295 @default.
- W4280599358 isParatext "false" @default.
- W4280599358 isRetracted "false" @default.
- W4280599358 workType "article" @default.