title: Flow cytometric determination of Src phosphorylation in pediatric patients treated with dasatinib.
abstract: Tyrosine kinase inhibitors, such as imatinib, have dramatically improved the outcomes for patients with selected cancers. For imatinib, western blotting of phospho-CrkL was an insensitive, indirect, and descriptive method to determine drug efficacy. Greater use of targeted therapies should involve more quantitative evaluation of the target's dose-inhibition. The Src/Abl kinase inhibitor dasatinib has recently been approved for use in Ph+ leukemias after failure with imatinib. Src family kinases (SFK) also play a critical role in nonhematologic cancers. We have developed a flow cytometric assay to measure SFK autophosphorylation levels in blood mononuclear cells and observed a direct correlation between its inhibition and patient dosage. This method provides a sensitive, quick, and quantitative tool to assess drug efficacy.
authors.affiliation: Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Bella S
authors.initials: BS
authors.lastname: Guerrouahen
authors.forename: Eric
authors.initials: E
authors.lastname: Wieder
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Blanchard
authors.forename: Francis Y
authors.initials: FY
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Corey
mesh_terms: D002648:Child; D000069439:Dasatinib; D005434:Flow Cytometry; D006801:Humans; D008722:Methods; D010766:Phosphorylation; D011743:Pyrimidines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D011743:Pyrimidines; D013844:Thiazoles; D019061:src-Family Kinases; D000069439:Dasatinib