Molecularly targeted treatment of chronic myeloid leukemia: beyond the imatinib era.
Chronic myeloid leukemia cells contain a BCR-ABL oncoprotein with an enhanced tyrosine kinase activity, which is considered to be the principal 'cause' of the leukemia. Though the precise mechanisms underlying the leukemogenesis remains enigmatic, the use of imatinib to inhibit the dysregulated kinase activity has proved remarkably successful in clinical practice. Imatinib was the first small molecule developed to inhibit BCR-ABL tyrosine kinase activity and its success introduced the current era of molecularly targeted therapies for a number of other malignancies. In patients with chronic myeloid leukaemia who develop resistance to imatinib, the Bcr-Abl signaling pathway is often re-established. This has led to the emergence of a number of alternative treatment strategies designed to target the leukemic cell which are resistant to imatinib.
Mughal
Tariq I
TI
Division of Hematology and Oncology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. tmughal@freenet.co.uk
Goldman
John M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D019496:Cancer Vaccines; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008954:Models, Biological; D008957:Models, Genetic; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011743:Pyrimidines / Q000627:therapeutic use*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D001549:Benzamides; D019496:Cancer Vaccines; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl