title: Novel aspects of therapy with the dual Src and Abl kinase inhibitor bosutinib in chronic myeloid leukemia.
abstract: The dual Src/Abl kinase inhibitor bosutinib (SKI-606) targets the tyrosine kinase brc-abl, the key enzyme in the development of chronic myeloid leukemia (CML). In clinical trials, bosutinib yielded promising results with regard to efficacy, tolerability and toxicity in first-, second- and third-line therapy of CML patients. Remarkably, bosutinib is able to overcome most imatinib-resistant BCR-ABL1-1 mutations except V299L and T315I. Mostly, low-to-moderate grade gastrointestinal toxicitis are the most common treatment-emergent adverse events observed under bosutinib. Unlike other tyrosine kinase inhibitors approved for CML treatment to date, bosutinib shows only minimal inhibitory activity against c-KIT and the PDGF receptor. This may be causative for its favorable hematologic toxicity profile. In this review, the authors give an overview on the mechanism of action and currently available preclinical and clinical data for bosutinib in CML.
authors.affiliation: Klinik für Hämatologie und Onkologie mit der Sektion Pneumologie, Onkologisches Zentrum, Universitäts-Klinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gunhild
authors.initials: G
authors.lastname: Keller-V Amsberg
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001549:Benzamides; D001682:Biological Availability; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D060735:Pharmacovigilance; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016032:Randomized Controlled Trials as Topic; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000814:Aniline Compounds; D001549:Benzamides; D009570:Nitriles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011804:Quinolines; C471992:bosutinib; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl