000009554 001__ 9554
000009554 005__ 20240415102343.0
000009554 0247_ $$2DOI$$a10.6083/xk81jm14w
000009554 037__ $$aIR
000009554 245__ $$aPredicting Imatinib responses in exon 18 PDGFRA-mutant GIST
000009554 260__ $$bOregon Health and Science University
000009554 269__ $$a2022
000009554 336__ $$aAbstract
000009554 520__ $$aThe majority of gastrointestinal stromal tumor (GIST) are driven by mutations in KIT or platelet derived growth factor receptor alpha (PDGFRA) receptor tyrosine kinases. Imatinib, a type II KIT/PDGFRA tyrosine kinase inhibitor (TKI), is the first-line treatment for advanced GIST. However, the most common PDGFRA mutation, exon 18 D842V, is strongly resistant to imatinib and other type II TKIs. Over 80% of unique PDGFRA mutations in GIST occur in exon 18, and they include many complexities such as in/dels and additional point mutations. It is largely unknown how these mutations respond to imatinib, but many are assumed to be resistant, like D842V. Contrary to these assumptions, we have shown in our in vitro models that some of these clinically observed exon 18 mutations were imatinib sensitive. Imatinib sensitivity also seemed to be dependent on the characteristics of the amino acid at the 842 position, which led us to hypothesize that sensitivity is largely determined by this residue. To test this hypothesis, we cloned and expressed every possible variant at the 842 position in Ba/F3 cells and determined imatinib sensitivity via immunoblotting.
000009554 540__ $$fCC BY
000009554 542__ $$fIn copyright - joint owners
000009554 650__ $$aSarcoma$$025711
000009554 650__ $$aDrug Resistance$$018079
000009554 650__ $$aNeoplasms$$022758
000009554 650__ $$aTyrosine Protein Kinase Inhibitors$$013842
000009554 650__ $$aGastrointestinal Stromal Tumors$$035784
000009554 650__ $$aImatinib Mesylate$$011313
000009554 6531_ $$acancer
000009554 6531_ $$aGIST
000009554 7001_ $$aKhosroyani, Homma M.$$uOregon Health and Science University$$041354
000009554 7001_ $$aHeinrich, Michael C.$$uOregon Health and Science University$$041354
000009554 711__ $$aResearch Week$$uOregon Health and Science University$$d2022
000009554 8564_ $$959d299cd-5ec1-4b37-820a-ca5e83ac1cc1$$s49749$$uhttps://digitalcollections.ohsu.edu/record/9554/files/Khosroyani-Homma-OHSU-ResearchWeek-2022.pdf
000009554 905__ $$a/rest/prod/xk/81/jm/14/xk81jm14w
000009554 980__ $$aResearch Week