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Last Findings on Dual Inhibitors of Abl and Src Tyrosine-Kinases

[ Vol. 7 , Issue. 2 ]

Author(s):

S. Schenone, F. Manetti and M. Botta   Pages 191 - 201 ( 11 )

Abstract:


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 hyperproliferation 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.

Keywords:

Chronic myelogenous leukemia, tyrosine kinases, Src, Bcr-Abl, dual inhibitors, Imatinib, resistance

Affiliation:

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV, I-16132, Genova, Italy.



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