title: Dasatinib for the treatment of Philadelphia chromosome-positive leukaemias.
abstract: BCR-ABL, a constitutively active tyrosine kinase, causes chronic myeloid leukaemia (CML). Rational development of drugs targeting BCR-ABL has significantly improved the treatment of CML. Imatinib (a BCR-ABL tyrosine kinase inhibitor) produces haematological and cytogenetic remissions across all phases of CML and is the present standard of care. Imatinib resistance occurs in a significant proportion of patients and mechanisms of resistance include BCR-ABL mutations and activation of alternate oncogenic pathways. Dasatinib is a novel, potent, multi-targeted oral kinase inhibitor. Preclinical and clinical investigations demonstrate that dasatinib effectively overcomes imatinib resistance and has further improved the treatment of CML. Dasatinib was recently approved by the FDA for use in Philadelphia-positive leukaemias in patients who are resistant or intolerant to imatinib.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Leukaemia, Box 428, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib