Matches in SemOpenAlex for { <https://semopenalex.org/work/W3094503775> ?p ?o ?g. }
- W3094503775 abstract "Abstract Molecularly targeted cancer therapy has improved outcomes for cancer patients with targetable oncoproteins, such as mutant epidermal growth factor receptor ( EGFR ) in lung cancer. Yet, long-term patient survival remains limited because treatment responses are typically incomplete. One potential explanation for the lack of complete and durable responses is that oncogene-driven cancers with activating mutations in the EGFR often harbor additional co-occurring genetic alterations. This hypothesis remains untested for most genetic alterations that co-occur with mutant EGFR . Here, we report the functional impact of inactivating genetic alteration of the mRNA splicing factor RBM10 that co-occur with mutant EGFR . RBM10 deficiency decreased EGFR inhibitor efficacy in patient-derived EGFR mutant tumor models. RBM10 modulated mRNA alternative splicing of the mitochondrial apoptotic regulator Bcl-x to regulate tumor cell apoptosis during treatment. Genetic inactivation of RBM10 diminished EGFR inhibitor-mediated apoptosis by decreasing the ratio of Bcl-xS-(pro-apoptotic)-to-Bcl-xL(anti-apoptotic) Bcl-x isoforms. RBM10 deficiency was a biomarker of poor response to EGFR inhibitor treatment in clinical samples. Co-inhibition of Bcl-xL and mutant EGFR overcame resistance induced by RBM10 deficiency. This study sheds light on the role of co-occurring genetic alterations, and on the impact of splicing factor deficiency in the modulation of sensitivity to targeted kinase inhibitor cancer therapy." @default.
- W3094503775 created "2020-10-29" @default.
- W3094503775 creator A5004509086 @default.
- W3094503775 creator A5004579069 @default.
- W3094503775 creator A5005008854 @default.
- W3094503775 creator A5010032300 @default.
- W3094503775 creator A5012288680 @default.
- W3094503775 creator A5015627096 @default.
- W3094503775 creator A5021107925 @default.
- W3094503775 creator A5044887899 @default.
- W3094503775 creator A5046077132 @default.
- W3094503775 creator A5046816554 @default.
- W3094503775 creator A5047587326 @default.
- W3094503775 creator A5053320236 @default.
- W3094503775 creator A5059811522 @default.
- W3094503775 creator A5063823247 @default.
- W3094503775 creator A5077718155 @default.
- W3094503775 creator A5084359163 @default.
- W3094503775 creator A5086191166 @default.
- W3094503775 creator A5088809839 @default.
- W3094503775 creator A5090738717 @default.
- W3094503775 date "2020-10-27" @default.
- W3094503775 modified "2023-10-08" @default.
- W3094503775 title "Deficiency of the splicing factor RBM10 limits EGFR inhibitor response in <i>EGFR</i> mutant lung cancer" @default.
- W3094503775 cites W1506037097 @default.
- W3094503775 cites W1983774108 @default.
- W3094503775 cites W1998971866 @default.
- W3094503775 cites W2003984225 @default.
- W3094503775 cites W2008757142 @default.
- W3094503775 cites W2017138237 @default.
- W3094503775 cites W2019607817 @default.
- W3094503775 cites W2042386784 @default.
- W3094503775 cites W2043058822 @default.
- W3094503775 cites W2067678773 @default.
- W3094503775 cites W2088540000 @default.
- W3094503775 cites W2091134276 @default.
- W3094503775 cites W2096198395 @default.
- W3094503775 cites W2099540110 @default.
- W3094503775 cites W2102088611 @default.
- W3094503775 cites W2111662961 @default.
- W3094503775 cites W2119351872 @default.
- W3094503775 cites W2123531506 @default.
- W3094503775 cites W2129360604 @default.
- W3094503775 cites W2129766349 @default.
- W3094503775 cites W2133609080 @default.
- W3094503775 cites W2143350291 @default.
- W3094503775 cites W2149441684 @default.
- W3094503775 cites W2158217645 @default.
- W3094503775 cites W2162574319 @default.
- W3094503775 cites W2168632005 @default.
- W3094503775 cites W2168841302 @default.
- W3094503775 cites W2180481128 @default.
- W3094503775 cites W2207020174 @default.
- W3094503775 cites W2268478667 @default.
- W3094503775 cites W2356766777 @default.
- W3094503775 cites W2524089049 @default.
- W3094503775 cites W2551781955 @default.
- W3094503775 cites W2553574746 @default.
- W3094503775 cites W2560624069 @default.
- W3094503775 cites W2578166854 @default.
- W3094503775 cites W2581103010 @default.
- W3094503775 cites W2766316939 @default.
- W3094503775 cites W2770828094 @default.
- W3094503775 cites W2772814465 @default.
- W3094503775 cites W2783397995 @default.
- W3094503775 cites W2795877840 @default.
- W3094503775 cites W2966767107 @default.
- W3094503775 cites W2969718750 @default.
- W3094503775 cites W3042475334 @default.
- W3094503775 doi "https://doi.org/10.1101/2020.10.26.356352" @default.
- W3094503775 hasPublicationYear "2020" @default.
- W3094503775 type Work @default.
- W3094503775 sameAs 3094503775 @default.
- W3094503775 citedByCount "1" @default.
- W3094503775 countsByYear W30945037752020 @default.
- W3094503775 crossrefType "posted-content" @default.
- W3094503775 hasAuthorship W3094503775A5004509086 @default.
- W3094503775 hasAuthorship W3094503775A5004579069 @default.
- W3094503775 hasAuthorship W3094503775A5005008854 @default.
- W3094503775 hasAuthorship W3094503775A5010032300 @default.
- W3094503775 hasAuthorship W3094503775A5012288680 @default.
- W3094503775 hasAuthorship W3094503775A5015627096 @default.
- W3094503775 hasAuthorship W3094503775A5021107925 @default.
- W3094503775 hasAuthorship W3094503775A5044887899 @default.
- W3094503775 hasAuthorship W3094503775A5046077132 @default.
- W3094503775 hasAuthorship W3094503775A5046816554 @default.
- W3094503775 hasAuthorship W3094503775A5047587326 @default.
- W3094503775 hasAuthorship W3094503775A5053320236 @default.
- W3094503775 hasAuthorship W3094503775A5059811522 @default.
- W3094503775 hasAuthorship W3094503775A5063823247 @default.
- W3094503775 hasAuthorship W3094503775A5077718155 @default.
- W3094503775 hasAuthorship W3094503775A5084359163 @default.
- W3094503775 hasAuthorship W3094503775A5086191166 @default.
- W3094503775 hasAuthorship W3094503775A5088809839 @default.
- W3094503775 hasAuthorship W3094503775A5090738717 @default.
- W3094503775 hasBestOaLocation W30945037751 @default.
- W3094503775 hasConcept C104317684 @default.
- W3094503775 hasConcept C121608353 @default.
- W3094503775 hasConcept C126322002 @default.
- W3094503775 hasConcept C143065580 @default.