SRCircumventing imatinib resistance.
The ABL inhibitor imatinib is a highly effective therapy for patients with chronic myeloid leukemia. Relapses after an initial response have been observed in some patients, and mutations of the BCR-ABL gene are the most common mechanism driving these relapses. Alternative ABL inhibitors have been identified that inhibit most of the common BCR-ABL mutations, and one has entered clinical trials. The structural basis for these results has yielded significant insights into the mechanism of action of these compounds, mechanisms of resistance, and their ability to inhibit the BCR-ABL mutants. These studies demonstrate the importance and impact of conducting scientific studies as part of clinical trials.
Deininger
Michael W N
MW
Oregon Health & Science University Cancer Institute, Center for Hematologic Malignancies, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Druker
Brian J
BJ
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001549:Benzamides; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism; D008958:Models, Molecular; D010879:Piperazines / Q000378:metabolism* / Q000627:therapeutic use; D011487:Protein Conformation; D011743:Pyrimidines / Q000378:metabolism* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl