Imatinib and chronic myeloid leukemia: validating the promise of molecularly targeted therapy.
The Bcr-Abl tyrosine kinase inhibitor imatinib (Glivec, formerly STI571, Novartis Pharma AG, Basel, Switzerland) produces complete hematologic and cytogenetic responses in a substantial percentage of chronic myeloid leukemia patients. Imatinib is effective in chronic phase, accelerated phase and blast crisis, with lower response rates in patients with more advanced disease. Although responses have been durable in chronic phase patients, relapses have been common in blast crisis. Relapse has been associated with reactivation of Bcr-Abl kinase activity. The clinical development of imatinib illustrates the effectiveness of targeting molecular pathogenetic events. Hopefully, this example can be extended to other malignancies.
Druker
Brian J
BJ
Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR 97201, USA. drukerb@ohsu.edu
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate