title: The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia.
abstract: Multiple small molecule kinase inhibitors are currently undergoing development for the treatment of acute myeloid leukemia (AML). Recently, selective and potent FLT3 inhibitors such as AC220 (quizartinib) have proven clinically effective in patients with AML with FLT3 internal tandem duplication (ITD) mutations, but inhibitors of other pathologically activated kinases in AML such as c-KIT and JAK2 have achieved less clinical success. Other classes of inhibitors currently undergoing clinical development target mediators of downstream signaling pathways such as mTOR and MEK or cell cycle machinery such as aurora kinases, PLK1, or cyclin-dependent kinases. Other than FLT3 inhibitors, most inhibitors have achieved only rare bone marrow responses, and kinase inhibitor therapy in AML remains investigational. Continuing efforts to develop kinase inhibitors for the treatment of AML will require careful selection of patients for clinical trials, translational studies to characterize responders, and investigation of combination therapy that may be capable of improving response rates and duration.
authors.affiliation: From the Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Smith
authors.forename: Neil P
authors.initials: NP
authors.lastname: Shah
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D052160:Benzothiazoles / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008938:Mitosis / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods*; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors
chemical_list: D052160:Benzothiazoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C544967:quizartinib; C546842:MTOR protein, human; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D058570:TOR Serine-Threonine Kinases