Nilotinib: a novel Bcr-Abl tyrosine kinase inhibitor for the treatment of leukemias.
The successful introduction of the tyrosine kinase inhibitors has initiated a new era in the management of chronic myeloid leukemia (CML). Imatinib mesilate therapy has significantly improved the prognosis of CML. A minority of patients in chronic-phase CML--and more patients in advanced phases--are resistant to imatinib, or develop resistance during treatment. This is attributed, in 40-50% of cases, to the development of mutations in the Bcr-Abl tyrosine kinase domain that impair imatinib binding. Nilotinib (Tasigna) is a novel potent selective oral kinase inhibitor. Preclinical and clinical investigations demonstrate that nilotinib effectively overcomes imatinib resistance, and has induced high rates of hematologic and cytogenetic responses in CML post imatinib failure.
Jabbour
Elias
E
The University of Texas, MD Anderson Cancer Center, Department of Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030, USA. ejabbour@mdanderson.org
El Ahdab
Samih
S
Cortes
Jorge
J
Kantarjian
Hagop
H
D000818:Animals; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib