Last findings on dual inhibitors of abl and SRC tyrosine-kinases.

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 pathol. of the disease. Targeted inhibitors of Bcr-Abl have antiproliferative effects on the leukemic cells and induce apoptosis, favoring 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 non-receptor tyrosine kinases, fundamental for cell development, growth, replication, adhesion, motility and is overexpressed in a wide no. 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 were recently synthesized and tested. This mini review will be focused on the latest finding on this matter.