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Title: Last findings on dual inhibitors of Abl and Src tyrosine-kinases
Authors: Schenone, S
Manetti, Fabrizio 
Botta, Maurizio 
Keywords: Bcr-Abl; Chronic myelogenous leukemia; Dual inhibitors; Imatinib; Resistance; Src; Tyrosine kinases
Issue Date: 2007
Project: None 
Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome that expresses the constitutively activated tyrosine kinase Bcr-Abl; this enzyme causes hyper-proliferation of the stem cells and the consequent pathology of the disease. Targeted inhibitors of Bcr-Abl have antiproliferative effects on the leukemic cells and induce apoptosis, favouring a regression of the CML chronic phase, but in the successive blast crisis phase cancer cells frequently develop resistance to Bcr-Abl inhibitors. Src is a family of nonreceptor tyrosine kinases, fundamental for cell development, growth, replication, adhesion, motility and is overexpressed in a wide number of human cancers. Recently it was demonstrated that Src is increased in hematopoietic cells expressing Bcr-Abl and is involved in the oncogenic pathway that causes CML. For this reason and also for the development of resistance to classical Bcr-Abl inhibitors, various dual Src/Abl inhibitors have been recently synthesized and tested. This mini review will be focused on the latest finding on this matter.
ISSN: 1389-5575
DOI: 10.2174/138955707779802598
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