Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361000377> ?p ?o ?g. }
- W4361000377 endingPage "2157" @default.
- W4361000377 startingPage "2144" @default.
- W4361000377 abstract "Abstract Purpose: To create an in vivo model of PDGFRA D842V-mutant gastrointestinal stromal tumor (GIST) and identify the mechanism of tumor persistence following avapritinib therapy. Experimental Design: We created a patient-derived xenograft (PDX) of PDGFRA D842V-mutant GIST and tested the effects of imatinib, avapritinib, and ML-7, an inhibitor of myosin light-chain kinase (MYLK). Bulk tumor RNA sequencing and oncogenic signaling were evaluated. Apoptosis, survival, and actin cytoskeleton were evaluated in GIST T1 cells and isolated PDX cells in vitro. Human GIST specimens were analyzed for MYLK expression. Results: The PDX was minimally responsive to imatinib but sensitive to avapritinib. Avapritinib therapy increased tumor expression of genes related to the actin cytoskeleton, including MYLK. ML-7 induced apoptosis and disrupted actin filaments in short-term cultures of PDX cells and decreased survival in GIST T1 cells in combination with imatinib or avapritinib. Combined therapy with ML-7 improved the antitumor effects of low-dose avapritinib in vivo. Furthermore, MYLK was expressed in human GIST specimens. Conclusions: MYLK upregulation is a novel mechanism of tumor persistence after tyrosine kinase inhibition. Concomitant MYLK inhibition may enable the use of a lower dose of avapritinib, which is associated with dose-dependent cognitive side effects." @default.
- W4361000377 created "2023-03-30" @default.
- W4361000377 creator A5002768993 @default.
- W4361000377 creator A5003185709 @default.
- W4361000377 creator A5009276894 @default.
- W4361000377 creator A5018185450 @default.
- W4361000377 creator A5021772683 @default.
- W4361000377 creator A5030081269 @default.
- W4361000377 creator A5038884384 @default.
- W4361000377 creator A5047039453 @default.
- W4361000377 creator A5051601236 @default.
- W4361000377 creator A5061152749 @default.
- W4361000377 creator A5061434147 @default.
- W4361000377 creator A5077200170 @default.
- W4361000377 creator A5086786876 @default.
- W4361000377 date "2023-03-27" @default.
- W4361000377 modified "2023-09-24" @default.
- W4361000377 title "Myosin Light-Chain Kinase Inhibition Potentiates the Antitumor Effects of Avapritinib in <i>PDGFRA D842V</i>-Mutant Gastrointestinal Stromal Tumor" @default.
- W4361000377 cites W1481712436 @default.
- W4361000377 cites W1596707465 @default.
- W4361000377 cites W1964708202 @default.
- W4361000377 cites W1976823322 @default.
- W4361000377 cites W1983814120 @default.
- W4361000377 cites W1987560705 @default.
- W4361000377 cites W1998687037 @default.
- W4361000377 cites W2005734249 @default.
- W4361000377 cites W2006124456 @default.
- W4361000377 cites W2018699957 @default.
- W4361000377 cites W2020005537 @default.
- W4361000377 cites W2031131470 @default.
- W4361000377 cites W2038272666 @default.
- W4361000377 cites W2044884083 @default.
- W4361000377 cites W2051330571 @default.
- W4361000377 cites W2082484368 @default.
- W4361000377 cites W2086968084 @default.
- W4361000377 cites W2101335366 @default.
- W4361000377 cites W2101986793 @default.
- W4361000377 cites W2102659321 @default.
- W4361000377 cites W2102769930 @default.
- W4361000377 cites W2103375442 @default.
- W4361000377 cites W2105266148 @default.
- W4361000377 cites W2106006357 @default.
- W4361000377 cites W2106631163 @default.
- W4361000377 cites W2107092244 @default.
- W4361000377 cites W2116098498 @default.
- W4361000377 cites W2129093214 @default.
- W4361000377 cites W2129282525 @default.
- W4361000377 cites W2138153563 @default.
- W4361000377 cites W2138231208 @default.
- W4361000377 cites W2140626630 @default.
- W4361000377 cites W2150501295 @default.
- W4361000377 cites W2171869961 @default.
- W4361000377 cites W223909586 @default.
- W4361000377 cites W2274026040 @default.
- W4361000377 cites W2416618462 @default.
- W4361000377 cites W2497332524 @default.
- W4361000377 cites W2619466966 @default.
- W4361000377 cites W2754132767 @default.
- W4361000377 cites W2755954269 @default.
- W4361000377 cites W2762504941 @default.
- W4361000377 cites W2767051969 @default.
- W4361000377 cites W2788530857 @default.
- W4361000377 cites W2891494402 @default.
- W4361000377 cites W2895684582 @default.
- W4361000377 cites W2913431000 @default.
- W4361000377 cites W3000675236 @default.
- W4361000377 cites W3033611734 @default.
- W4361000377 cites W3037595396 @default.
- W4361000377 cites W3088256583 @default.
- W4361000377 cites W3121915712 @default.
- W4361000377 cites W3137417877 @default.
- W4361000377 cites W4206679340 @default.
- W4361000377 doi "https://doi.org/10.1158/1078-0432.ccr-22-0533" @default.
- W4361000377 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36971786" @default.
- W4361000377 hasPublicationYear "2023" @default.
- W4361000377 type Work @default.
- W4361000377 citedByCount "0" @default.
- W4361000377 crossrefType "journal-article" @default.
- W4361000377 hasAuthorship W4361000377A5002768993 @default.
- W4361000377 hasAuthorship W4361000377A5003185709 @default.
- W4361000377 hasAuthorship W4361000377A5009276894 @default.
- W4361000377 hasAuthorship W4361000377A5018185450 @default.
- W4361000377 hasAuthorship W4361000377A5021772683 @default.
- W4361000377 hasAuthorship W4361000377A5030081269 @default.
- W4361000377 hasAuthorship W4361000377A5038884384 @default.
- W4361000377 hasAuthorship W4361000377A5047039453 @default.
- W4361000377 hasAuthorship W4361000377A5051601236 @default.
- W4361000377 hasAuthorship W4361000377A5061152749 @default.
- W4361000377 hasAuthorship W4361000377A5061434147 @default.
- W4361000377 hasAuthorship W4361000377A5077200170 @default.
- W4361000377 hasAuthorship W4361000377A5086786876 @default.
- W4361000377 hasBestOaLocation W43610003772 @default.
- W4361000377 hasConcept C121608353 @default.
- W4361000377 hasConcept C16930146 @default.
- W4361000377 hasConcept C2775922572 @default.
- W4361000377 hasConcept C2777007597 @default.
- W4361000377 hasConcept C2777583451 @default.
- W4361000377 hasConcept C2778729363 @default.