FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2891037237> ?p ?o ?g. }

• W2891037237 abstract "e23150 Background: HER2 variants are implicated as oncogenic drivers in a variety of cancers. However, not all HER2 variants found on next-generation sequencing (NGS) have been studied, raising the question if these variants of unknown significance (VUS) are oncogenic. This study explores the use of an in-vitro functional assay on HER2 and other variants found on NGS in patients (pts) with lung cancer, and its predictive value for response to HER2 targeted therapy. Methods: Pts with lung cancer at Memorial Sloan Kettering identified to have a HER2 variant by NGS on MSK IMPACT are eligible. NGS data on HER2 variants and co-mutations were analyzed. Functional status was determined by the NovellusDx FACT platform. Mutations were synthesized and transfected into HeLa cells with a fluorescently tagged signaling pathway reporter (MAPK, NFKB, JAK-STAT). Fluorescent microscopy quantified the translocation of reporters to the nucleus, inferring gain of function. Afatinib was added and its effect on pathway activation analyzed. Functional information was correlated with clinical outcomes. Results: As of 2/1/17, 13 pts were included, 9 unique HER2 variants analyzed. Known activating HER2 mutations analyzed (exon 20 insertions (A775_G776insYVMA, G778_P780insGSP, G776delinsVC), point mutations (V659E, L755P, S301F)) showed in vitro gain of function. HER2 VUS analyzed included D277Y showed no gain of function; exon 16 splice variant c.1889 showed gain of function. Afatinib was added to 4 cell lines with gain of function variants (G778_P780insGSP, V659E, L755P, exon 16 splice variant c.1889) all had inhibited pathway activation suggesting in vitro sensitivity to afatinib. Clinically, no response was seen in 2 pts treated with afatinib but more pts are planned to be treated. Objective responses to ado-trastuzumab emtansine (NCT02675829) were seen in 5 pts, all of which had HER2 variants with gain of function. Conclusions: In vitro functional analysis of HER2 variants based on NGS reports is feasible, and has the potential to identify novel actionable oncogenic drivers from VUS. Its predictive value for clinical response to targeted therapy requires further study." @default.
• W2891037237 created "2018-09-27" @default.
• W2891037237 creator A5004235659 @default.
• W2891037237 creator A5004538056 @default.
• W2891037237 creator A5005236939 @default.
• W2891037237 creator A5006697352 @default.
• W2891037237 creator A5010046486 @default.
• W2891037237 creator A5016977043 @default.
• W2891037237 creator A5020223489 @default.
• W2891037237 creator A5024203424 @default.
• W2891037237 creator A5039791495 @default.
• W2891037237 creator A5042115782 @default.
• W2891037237 creator A5049524331 @default.
• W2891037237 creator A5053263729 @default.
• W2891037237 creator A5077401586 @default.
• W2891037237 creator A5081273660 @default.
• W2891037237 date "2017-05-20" @default.
• W2891037237 modified "2023-09-27" @default.
• W2891037237 title "In vitro functional analysis of HER2 variants in lung cancers to evaluate their oncogenic activity and predict clinical response to HER2 targeted therapies." @default.
• W2891037237 doi "https://doi.org/10.1200/jco.2017.35.15_suppl.e23150" @default.
• W2891037237 hasPublicationYear "2017" @default.
• W2891037237 type Work @default.
• W2891037237 sameAs 2891037237 @default.
• W2891037237 citedByCount "0" @default.
• W2891037237 crossrefType "journal-article" @default.
• W2891037237 hasAuthorship W2891037237A5004235659 @default.
• W2891037237 hasAuthorship W2891037237A5004538056 @default.
• W2891037237 hasAuthorship W2891037237A5005236939 @default.
• W2891037237 hasAuthorship W2891037237A5006697352 @default.
• W2891037237 hasAuthorship W2891037237A5010046486 @default.
• W2891037237 hasAuthorship W2891037237A5016977043 @default.
• W2891037237 hasAuthorship W2891037237A5020223489 @default.
• W2891037237 hasAuthorship W2891037237A5024203424 @default.
• W2891037237 hasAuthorship W2891037237A5039791495 @default.
• W2891037237 hasAuthorship W2891037237A5042115782 @default.
• W2891037237 hasAuthorship W2891037237A5049524331 @default.
• W2891037237 hasAuthorship W2891037237A5053263729 @default.
• W2891037237 hasAuthorship W2891037237A5077401586 @default.
• W2891037237 hasAuthorship W2891037237A5081273660 @default.
• W2891037237 hasConcept C143998085 @default.
• W2891037237 hasConcept C202751555 @default.
• W2891037237 hasConcept C2776256026 @default.
• W2891037237 hasConcept C502942594 @default.
• W2891037237 hasConcept C54355233 @default.
• W2891037237 hasConcept C71924100 @default.
• W2891037237 hasConcept C86803240 @default.
• W2891037237 hasConceptScore W2891037237C143998085 @default.
• W2891037237 hasConceptScore W2891037237C202751555 @default.
• W2891037237 hasConceptScore W2891037237C2776256026 @default.
• W2891037237 hasConceptScore W2891037237C502942594 @default.
• W2891037237 hasConceptScore W2891037237C54355233 @default.
• W2891037237 hasConceptScore W2891037237C71924100 @default.
• W2891037237 hasConceptScore W2891037237C86803240 @default.
• W2891037237 hasLocation W28910372371 @default.
• W2891037237 hasOpenAccess W2891037237 @default.
• W2891037237 hasPrimaryLocation W28910372371 @default.
• W2891037237 hasRelatedWork W1598707954 @default.
• W2891037237 hasRelatedWork W1676117227 @default.
• W2891037237 hasRelatedWork W1949953198 @default.
• W2891037237 hasRelatedWork W2055794799 @default.
• W2891037237 hasRelatedWork W2076647600 @default.
• W2891037237 hasRelatedWork W2097823004 @default.
• W2891037237 hasRelatedWork W2122766813 @default.
• W2891037237 hasRelatedWork W2283148074 @default.
• W2891037237 hasRelatedWork W2395930819 @default.
• W2891037237 hasRelatedWork W2460590704 @default.
• W2891037237 hasRelatedWork W2781852111 @default.
• W2891037237 hasRelatedWork W2915496604 @default.
• W2891037237 hasRelatedWork W2961375208 @default.
• W2891037237 hasRelatedWork W3009512811 @default.
• W2891037237 hasRelatedWork W3010457537 @default.
• W2891037237 hasRelatedWork W3029743090 @default.
• W2891037237 hasRelatedWork W3032198943 @default.
• W2891037237 hasRelatedWork W3093809873 @default.
• W2891037237 hasRelatedWork W3120155456 @default.
• W2891037237 hasRelatedWork W3126704571 @default.
• W2891037237 isParatext "false" @default.
• W2891037237 isRetracted "false" @default.
• W2891037237 magId "2891037237" @default.
• W2891037237 workType "article" @default.