title: Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia as a model of rational drug design in cancer.
abstract: Many biological and clinical features of chronic myeloid leukemia make it as a paradigm of rational drug design in human cancer. Chronic myeloid leukemia was the first malignancy to be linked to a clear genetic anomaly, the Philadelphia chromosome and, at present, it is probably the best understood of all human malignancies. Studies of the disease pathology revealed that the molecular consequence of the Philadelphia translocation is a BCR-ABL chimeric gene, which encodes a constitutively active tyrosine kinase with wholesale range of biological activities. Animal models have validated the direct role of the BCR-ABL protein in malignant transformation and subsequent research confirmed that its enhanced tyrosine kinase activity is essential and sufficient for the leukemogenesis. The very existence of a single genetic abnormality, presented in essentially all patients with the disease, made it an effective target for molecularly designed therapeutic approaches for the disease. The advent of tyrosine kinase inhibitors, designed specifically to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein, represents one of the major innovations in cancer therapy and may serve as a model for, how discoveries of disease pathogenesis may be translated into the development of successful targeted therapies in cancer medicine.
authors.affiliation: Department of Hematology, Kuwait Cancer Control Center, Shuwaikh, Kuwait. annaadria@yahoo.com
authors.forename: Adriana
authors.initials: A
authors.lastname: Zámečníkova
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002877:Chromosomes, Human; D015195:Drug Design; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl