Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361958289> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W4361958289 abstract "<div>AbstractPurpose:<p>Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive form of NSCLC. Rarity and poor characterization have limited the development of PSC-tailored treatment protocols, leaving patients with inadequate therapeutic options. In this study, we investigated the gene expression profile of PSCs, with the aim to characterize the molecular mechanisms responsible for their evolution and to identify new drugs for their treatment.</p>Experimental Design:<p>A training set of 17 biphasic PSCs was selected and tested for the expression of a large panel of 770 genes related to cancer progression using NanoString technology. Computational analyses were used to characterize a PSCs-gene specific signature from which pathways and drivers of PSC evolution were identified and validated using functional assays in vitro. This signature was validated in a separate set of 15 PSCs and 8 differentiated NSCLC and used to interrogate the cMAP database searching for FDA-approved small molecules able to counteract PSC phenotype.</p>Results:<p>We demonstrated that the transcriptional activation of an epithelial mesenchymal transition (EMT) program drives PSC phylogeny <i>in vivo</i>. We showed that loss of the epithelial-associated transcription factor (TF) OVOL2 characterizes the transition to sarcomatoid phenotype triggering the expression of EMT promoting TFs, including TWIST and ZEB and the expression of the membrane kinase DDR2. Finally, using a drug repurposing approach, we identified dasatinib as potential inhibitor of the PSC-gene expression signature and we confirmed <i>in vitro</i> that this drug efficiently restrains proliferation and reverts the sarcomatoid-associated phenotype.</p>Conclusions:<p>Our data provide new insights into PSC evolution and provide the rationale for further clinical studies with dasatinib.</p></div>" @default.
- W4361958289 created "2023-04-05" @default.
- W4361958289 creator A5006279666 @default.
- W4361958289 creator A5014045886 @default.
- W4361958289 creator A5020969433 @default.
- W4361958289 creator A5042559824 @default.
- W4361958289 creator A5043896307 @default.
- W4361958289 creator A5051378203 @default.
- W4361958289 creator A5060916338 @default.
- W4361958289 creator A5089969449 @default.
- W4361958289 date "2023-03-31" @default.
- W4361958289 modified "2023-09-26" @default.
- W4361958289 title "Data from An Epithelial-to-Mesenchymal Transcriptional Switch Triggers Evolution of Pulmonary Sarcomatoid Carcinoma (PSC) and Identifies Dasatinib as New Therapeutic Option" @default.
- W4361958289 doi "https://doi.org/10.1158/1078-0432.c.6528408.v1" @default.
- W4361958289 hasPublicationYear "2023" @default.
- W4361958289 type Work @default.
- W4361958289 citedByCount "0" @default.
- W4361958289 crossrefType "posted-content" @default.
- W4361958289 hasAuthorship W4361958289A5006279666 @default.
- W4361958289 hasAuthorship W4361958289A5014045886 @default.
- W4361958289 hasAuthorship W4361958289A5020969433 @default.
- W4361958289 hasAuthorship W4361958289A5042559824 @default.
- W4361958289 hasAuthorship W4361958289A5043896307 @default.
- W4361958289 hasAuthorship W4361958289A5051378203 @default.
- W4361958289 hasAuthorship W4361958289A5060916338 @default.
- W4361958289 hasAuthorship W4361958289A5089969449 @default.
- W4361958289 hasConcept C104317684 @default.
- W4361958289 hasConcept C127561419 @default.
- W4361958289 hasConcept C127716648 @default.
- W4361958289 hasConcept C150194340 @default.
- W4361958289 hasConcept C162317418 @default.
- W4361958289 hasConcept C18431079 @default.
- W4361958289 hasConcept C2777583451 @default.
- W4361958289 hasConcept C2778729363 @default.
- W4361958289 hasConcept C2779536868 @default.
- W4361958289 hasConcept C2779733811 @default.
- W4361958289 hasConcept C502942594 @default.
- W4361958289 hasConcept C54355233 @default.
- W4361958289 hasConcept C76419328 @default.
- W4361958289 hasConcept C86339819 @default.
- W4361958289 hasConcept C86803240 @default.
- W4361958289 hasConceptScore W4361958289C104317684 @default.
- W4361958289 hasConceptScore W4361958289C127561419 @default.
- W4361958289 hasConceptScore W4361958289C127716648 @default.
- W4361958289 hasConceptScore W4361958289C150194340 @default.
- W4361958289 hasConceptScore W4361958289C162317418 @default.
- W4361958289 hasConceptScore W4361958289C18431079 @default.
- W4361958289 hasConceptScore W4361958289C2777583451 @default.
- W4361958289 hasConceptScore W4361958289C2778729363 @default.
- W4361958289 hasConceptScore W4361958289C2779536868 @default.
- W4361958289 hasConceptScore W4361958289C2779733811 @default.
- W4361958289 hasConceptScore W4361958289C502942594 @default.
- W4361958289 hasConceptScore W4361958289C54355233 @default.
- W4361958289 hasConceptScore W4361958289C76419328 @default.
- W4361958289 hasConceptScore W4361958289C86339819 @default.
- W4361958289 hasConceptScore W4361958289C86803240 @default.
- W4361958289 hasLocation W43619582891 @default.
- W4361958289 hasOpenAccess W4361958289 @default.
- W4361958289 hasPrimaryLocation W43619582891 @default.
- W4361958289 hasRelatedWork W1971124177 @default.
- W4361958289 hasRelatedWork W1985116998 @default.
- W4361958289 hasRelatedWork W1985562003 @default.
- W4361958289 hasRelatedWork W2093877942 @default.
- W4361958289 hasRelatedWork W2563598809 @default.
- W4361958289 hasRelatedWork W2734403094 @default.
- W4361958289 hasRelatedWork W3012091774 @default.
- W4361958289 hasRelatedWork W4213265720 @default.
- W4361958289 hasRelatedWork W4224439911 @default.
- W4361958289 hasRelatedWork W4294954873 @default.
- W4361958289 isParatext "false" @default.
- W4361958289 isRetracted "false" @default.
- W4361958289 workType "article" @default.