{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hahn CK"],"funding":["Howard Hughes Medical Institute","NCI NIH HHS"],"pagination":["281-94"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2803063"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(4)"],"pubmed_abstract":["Cell-based screening can facilitate the rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires the identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target, anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer."],"journal":["Cancer cell"],"pubmed_title":["Proteomic and genetic approaches identify Syk as an AML target."],"pmcid":["PMC2803063"],"funding_grant_id":["5K08 CA098444","K08 CA098444-05","K08 CA098444"],"pubmed_authors":["Stegmaier K","Clauser K","Silver SJ","Berchuck JE","Root DE","Galinsky I","Carroll M","Schinzel AC","Stone RM","DeAngelo DJ","Carr SA","Davis TN","Ross KN","Ross L","Hahn CK","Kakoza RM","Golub TR","Hahn WC","Kung AL"],"additional_accession":[]},"is_claimable":false,"name":"Proteomic and genetic approaches identify Syk as an AML target.","description":"Cell-based screening can facilitate the rapid identification of compounds inducing complex cellular phenotypes. Advancing a compound toward the clinic, however, generally requires the identification of precise mechanisms of action. We previously found that epidermal growth factor receptor (EGFR) inhibitors induce acute myeloid leukemia (AML) differentiation via a non-EGFR mechanism. In this report, we integrated proteomic and RNAi-based strategies to identify their off-target, anti-AML mechanism. These orthogonal approaches identified Syk as a target in AML. Genetic and pharmacological inactivation of Syk with a drug in clinical trial for other indications promoted differentiation of AML cells and attenuated leukemia growth in vivo. These results demonstrate the power of integrating diverse chemical, proteomic, and genomic screening approaches to identify therapeutic strategies for cancer.","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 Oct","modification":"2020-11-01T08:18:03Z","creation":"2019-03-27T00:27:47Z"},"accession":"S-EPMC2803063","cross_references":{"pubmed":["19800574"],"doi":["10.1016/j.ccr.2009.08.018"]}}