title: [Signal transduction inhibitor--STI571--a new treatment for chronic myeloid leukemia (CML), which opens a new targeted approach to cancer therapy].
abstract: Chronic myeloid leukemia (CML), in most of the cases, is the molecular consequence of the t(9,22) translocation, resulting in the Philadelphia (Ph) chromosome and the creation of the fusion gene BCR-ABL. The fusion gene is translated to the protooncogen BCR-ABL, a constitutively activated tyrosine kinase that is linked to the malignant transformation. Thus, this tyrosine kinase became an attractive target for drug design. The development of the novel investigational drug STI 571 is based on its potent and selective ability to inhibit this fusion tyrosine kinase. In preclinical studies, STI 571 selectively inhibited the growth of CML cells that carry the Ph chromosome. In this review we discuss the drug development and design, its mechanism of action, the preclinical studies and the results of phase I and II clinical trials.
authors.affiliation: Institute of Hematology, Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Nadav
authors.forename: Amiram
authors.initials: A
authors.lastname: Eldor
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; 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*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl