FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2316516629> ?p ?o ?g. }

• W2316516629 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCIntroduction: The Epidermal Growth Factor Receptor (EGFR) features prominently in malignant glioma (MG), yet attempts to exploit this target in patients with MG have been somewhat disappointing. Unlike the highly sensitizing kinase site alleles of EGFR derived from patients with non-small cell lung cancer (NSCLCA), mutationally activated alleles of EGFR derived from patients with MG respond poorly to the currently available reversible clinical EGFR inhibitors. We hypothesize that the anti-tumor effects of EGFR inhibitors in MG-associated alleles of EGFR require more efficient blockade to achieve anti-tumor responses, in comparison with NSCLCA-associated alleles of EGFR, and that thisincreased efficiency can be achieved using irreversible inhibitors.Methods: We generated glioma and fibroblast cell lines that expressed wild-type or tumor-associated alleles of EGFR derived either from MG (EGFRvIII) or NSCLCA (L858R or del 747-753). Using an EGFR affinity probe (an irreversible EGFR inhibitor tethered to a flourophore), we quantified occupancy of the kinase active site in response to erotinib, a clinical reversible inhibitor of EGFR, correlating occupancy with proliferation and apoptosis. Next, we repeated these measurements using the tool compound and irreversible EGFR inhibitor PD-168394.Results: Using the affinity probe in pulse-chase experiments, we quantified active site occupancy of EGFR int response to increasing doses of inhibitors. In cells expressing MG-derived alleles, irreversible EGFR inhibitors were significantly more potent than reversible agents in abrogating signaling downstream of EGFR and in decreasing viability. Using the affinity probe, we found that irreversible inhibitors showed nearly complete occupancy of the active site, whereas treatment with reversible EGFR inhibitors resulted in only partial occupancy. Cells containing NSCLCA-derived EGFR alleles showed similar signaling and growth responses to both reversible and EGFR inhibitors, despite a large difference in EGFR kinase site occupancy with the two types of inhibitors. Flow cytometry studies correlating kinase site occupancy with downstream signaling in individual cells will also be presented.Conclusions: Activated alleles of EGFR derived from MG require significantly higher levels of kinase site blockade to achieve an anti-proliferative threshold, as compared with activated alleles derived from NSCLCA. This higher degree of kinase site blockade can be achieved using irreversible inhibitors of EGFR. These studies support the initiation of clinical trials using irreversible inhibitors of EGFR in MG.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1973." @default.
• W2316516629 created "2016-06-24" @default.
• W2316516629 creator A5011191639 @default.
• W2316516629 creator A5020508182 @default.
• W2316516629 creator A5040646987 @default.
• W2316516629 creator A5073603294 @default.
• W2316516629 creator A5079376363 @default.
• W2316516629 creator A5079841820 @default.
• W2316516629 creator A5090555697 @default.
• W2316516629 date "2010-04-15" @default.
• W2316516629 modified "2023-09-25" @default.
• W2316516629 title "Abstract 1973: Targeting activated alleles of EGFR derived from glioma and lung cancer: Correlating kinase active-site occupancy with efficacy" @default.
• W2316516629 doi "https://doi.org/10.1158/1538-7445.am10-1973" @default.
• W2316516629 hasPublicationYear "2010" @default.
• W2316516629 type Work @default.
• W2316516629 sameAs 2316516629 @default.
• W2316516629 citedByCount "0" @default.
• W2316516629 crossrefType "proceedings-article" @default.
• W2316516629 hasAuthorship W2316516629A5011191639 @default.
• W2316516629 hasAuthorship W2316516629A5020508182 @default.
• W2316516629 hasAuthorship W2316516629A5040646987 @default.
• W2316516629 hasAuthorship W2316516629A5073603294 @default.
• W2316516629 hasAuthorship W2316516629A5079376363 @default.
• W2316516629 hasAuthorship W2316516629A5079841820 @default.
• W2316516629 hasAuthorship W2316516629A5090555697 @default.
• W2316516629 hasConcept C104317684 @default.
• W2316516629 hasConcept C121608353 @default.
• W2316516629 hasConcept C126322002 @default.
• W2316516629 hasConcept C142724271 @default.
• W2316516629 hasConcept C180754005 @default.
• W2316516629 hasConcept C184235292 @default.
• W2316516629 hasConcept C2776256026 @default.
• W2316516629 hasConcept C2777506169 @default.
• W2316516629 hasConcept C2778227246 @default.
• W2316516629 hasConcept C2779438470 @default.
• W2316516629 hasConcept C502942594 @default.
• W2316516629 hasConcept C55493867 @default.
• W2316516629 hasConcept C71924100 @default.
• W2316516629 hasConcept C86803240 @default.
• W2316516629 hasConcept C95444343 @default.
• W2316516629 hasConceptScore W2316516629C104317684 @default.
• W2316516629 hasConceptScore W2316516629C121608353 @default.
• W2316516629 hasConceptScore W2316516629C126322002 @default.
• W2316516629 hasConceptScore W2316516629C142724271 @default.
• W2316516629 hasConceptScore W2316516629C180754005 @default.
• W2316516629 hasConceptScore W2316516629C184235292 @default.
• W2316516629 hasConceptScore W2316516629C2776256026 @default.
• W2316516629 hasConceptScore W2316516629C2777506169 @default.
• W2316516629 hasConceptScore W2316516629C2778227246 @default.
• W2316516629 hasConceptScore W2316516629C2779438470 @default.
• W2316516629 hasConceptScore W2316516629C502942594 @default.
• W2316516629 hasConceptScore W2316516629C55493867 @default.
• W2316516629 hasConceptScore W2316516629C71924100 @default.
• W2316516629 hasConceptScore W2316516629C86803240 @default.
• W2316516629 hasConceptScore W2316516629C95444343 @default.
• W2316516629 hasLocation W23165166291 @default.
• W2316516629 hasOpenAccess W2316516629 @default.
• W2316516629 hasPrimaryLocation W23165166291 @default.
• W2316516629 hasRelatedWork W1821945583 @default.
• W2316516629 hasRelatedWork W1980984439 @default.
• W2316516629 hasRelatedWork W1991580010 @default.
• W2316516629 hasRelatedWork W1998344649 @default.
• W2316516629 hasRelatedWork W2028446584 @default.
• W2316516629 hasRelatedWork W2039178120 @default.
• W2316516629 hasRelatedWork W2060723055 @default.
• W2316516629 hasRelatedWork W2094111402 @default.
• W2316516629 hasRelatedWork W2097775552 @default.
• W2316516629 hasRelatedWork W2123441822 @default.
• W2316516629 hasRelatedWork W2200479345 @default.
• W2316516629 hasRelatedWork W2488622084 @default.
• W2316516629 hasRelatedWork W2553214361 @default.
• W2316516629 hasRelatedWork W2752953293 @default.
• W2316516629 hasRelatedWork W2810406187 @default.
• W2316516629 hasRelatedWork W2953930977 @default.
• W2316516629 hasRelatedWork W2954344000 @default.
• W2316516629 hasRelatedWork W3024740892 @default.
• W2316516629 hasRelatedWork W3035982534 @default.
• W2316516629 hasRelatedWork W3111867087 @default.
• W2316516629 isParatext "false" @default.
• W2316516629 isRetracted "false" @default.
• W2316516629 magId "2316516629" @default.
• W2316516629 workType "article" @default.