Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361945399> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W4361945399 abstract "<div>Abstract<p><b>Purpose:</b> The <i>BIM</i> deletion polymorphism is associated with apoptosis resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and erlotinib, in non–small cell lung cancer (NSCLC) harboring <i>EGFR</i> mutations. Here, we investigated whether the <i>BIM</i> deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism.</p><p><b>Experimental Design:</b> We used <i>EGFR</i>-mutated NSCLC cell lines, which were either heterozygous or homozygous for the <i>BIM</i> deletion polymorphism, to evaluate the effect of osimertinib <i>in vitro</i> and <i>in vivo</i>. Protein expression was examined by Western blotting. Alternative splicing of <i>BIM</i> mRNA was analyzed by RT-PCR.</p><p><b>Results:</b> <i>EGFR</i>-mutated NSCLC cell lines with the <i>BIM</i> deletion polymorphism exhibited apoptosis resistance to osimertinib in a polymorphism dosage–dependent manner, and this resistance was overcome by combined use with vorinostat. Experiments with homozygous <i>BIM</i> deletion–positive cells revealed that vorinostat affected the alternative splicing of <i>BIM</i> mRNA in the deletion allele, increased the expression of active BIM protein, and thereby induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. In xenograft models, combined use of vorinostat with osimertinib could regress tumors in <i>EGFR</i>-mutated NSCLC cells homozygous for the <i>BIM</i> deletion polymorphism. Moreover, this combination could induce apoptosis even when tumor cells acquired <i>EGFR</i>-T790M mutations.</p><p><b>Conclusions:</b> These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating <i>EGFR</i>-mutated lung cancers carrying the <i>BIM</i> deletion polymorphism. <i>Clin Cancer Res; 23(12); 3139–49. ©2016 AACR</i>.</p></div>" @default.
- W4361945399 created "2023-04-05" @default.
- W4361945399 creator A5006507911 @default.
- W4361945399 creator A5012416582 @default.
- W4361945399 creator A5017882443 @default.
- W4361945399 creator A5045660079 @default.
- W4361945399 creator A5061029876 @default.
- W4361945399 creator A5073598073 @default.
- W4361945399 creator A5086218839 @default.
- W4361945399 creator A5089982517 @default.
- W4361945399 date "2023-03-31" @default.
- W4361945399 modified "2023-10-14" @default.
- W4361945399 title "Data from Histone Deacetylase 3 Inhibition Overcomes <i>BIM</i> Deletion Polymorphism–Mediated Osimertinib Resistance in <i>EGFR-</i>Mutant Lung Cancer" @default.
- W4361945399 doi "https://doi.org/10.1158/1078-0432.c.6525318" @default.
- W4361945399 hasPublicationYear "2023" @default.
- W4361945399 type Work @default.
- W4361945399 citedByCount "0" @default.
- W4361945399 crossrefType "posted-content" @default.
- W4361945399 hasAuthorship W4361945399A5006507911 @default.
- W4361945399 hasAuthorship W4361945399A5012416582 @default.
- W4361945399 hasAuthorship W4361945399A5017882443 @default.
- W4361945399 hasAuthorship W4361945399A5045660079 @default.
- W4361945399 hasAuthorship W4361945399A5061029876 @default.
- W4361945399 hasAuthorship W4361945399A5073598073 @default.
- W4361945399 hasAuthorship W4361945399A5086218839 @default.
- W4361945399 hasAuthorship W4361945399A5089982517 @default.
- W4361945399 hasBestOaLocation W43619453992 @default.
- W4361945399 hasConcept C104317684 @default.
- W4361945399 hasConcept C121608353 @default.
- W4361945399 hasConcept C126322002 @default.
- W4361945399 hasConcept C13721689 @default.
- W4361945399 hasConcept C153911025 @default.
- W4361945399 hasConcept C185592680 @default.
- W4361945399 hasConcept C190283241 @default.
- W4361945399 hasConcept C2776256026 @default.
- W4361945399 hasConcept C2776262904 @default.
- W4361945399 hasConcept C2777626846 @default.
- W4361945399 hasConcept C2778087573 @default.
- W4361945399 hasConcept C2778305200 @default.
- W4361945399 hasConcept C2779438470 @default.
- W4361945399 hasConcept C2780580887 @default.
- W4361945399 hasConcept C502942594 @default.
- W4361945399 hasConcept C54355233 @default.
- W4361945399 hasConcept C55493867 @default.
- W4361945399 hasConcept C64927066 @default.
- W4361945399 hasConcept C71924100 @default.
- W4361945399 hasConcept C86803240 @default.
- W4361945399 hasConceptScore W4361945399C104317684 @default.
- W4361945399 hasConceptScore W4361945399C121608353 @default.
- W4361945399 hasConceptScore W4361945399C126322002 @default.
- W4361945399 hasConceptScore W4361945399C13721689 @default.
- W4361945399 hasConceptScore W4361945399C153911025 @default.
- W4361945399 hasConceptScore W4361945399C185592680 @default.
- W4361945399 hasConceptScore W4361945399C190283241 @default.
- W4361945399 hasConceptScore W4361945399C2776256026 @default.
- W4361945399 hasConceptScore W4361945399C2776262904 @default.
- W4361945399 hasConceptScore W4361945399C2777626846 @default.
- W4361945399 hasConceptScore W4361945399C2778087573 @default.
- W4361945399 hasConceptScore W4361945399C2778305200 @default.
- W4361945399 hasConceptScore W4361945399C2779438470 @default.
- W4361945399 hasConceptScore W4361945399C2780580887 @default.
- W4361945399 hasConceptScore W4361945399C502942594 @default.
- W4361945399 hasConceptScore W4361945399C54355233 @default.
- W4361945399 hasConceptScore W4361945399C55493867 @default.
- W4361945399 hasConceptScore W4361945399C64927066 @default.
- W4361945399 hasConceptScore W4361945399C71924100 @default.
- W4361945399 hasConceptScore W4361945399C86803240 @default.
- W4361945399 hasLocation W43619453991 @default.
- W4361945399 hasLocation W43619453992 @default.
- W4361945399 hasOpenAccess W4361945399 @default.
- W4361945399 hasPrimaryLocation W43619453991 @default.
- W4361945399 hasRelatedWork W2566097899 @default.
- W4361945399 hasRelatedWork W2741286634 @default.
- W4361945399 hasRelatedWork W2822334320 @default.
- W4361945399 hasRelatedWork W2906324362 @default.
- W4361945399 hasRelatedWork W3138677963 @default.
- W4361945399 hasRelatedWork W4324344390 @default.
- W4361945399 hasRelatedWork W4361920932 @default.
- W4361945399 hasRelatedWork W4361945399 @default.
- W4361945399 hasRelatedWork W4361952115 @default.
- W4361945399 hasRelatedWork W4362400726 @default.
- W4361945399 isParatext "false" @default.
- W4361945399 isRetracted "false" @default.
- W4361945399 workType "article" @default.