Signal Transduction Inhibitors in Chronic Myeloid Leukemia

摘要: Chronic myeloid leukemia (CML) is caused by Bcr-Abl, a constitutively active tyrosine kinase that activates multiple signaling pathways and central to disease pathogenesis. Efforts develop small molecule Bcr-Abl inhibitors led the discovery of imatinib, 2-phenylaminopyrimidine inhibits with high selectivity has rapidly become standard therapy for CML. Responses in newly diagnosed chronic phase patients tend be durable, but there relapse rate advanced disease, which mostly due point mutations critical residues interfere drug binding, thereby reactivating Bcr-Abl. The fact remains pathogenesis stimulated search novel Abl activity against mutant Nilotinib, developed from an imatinib backbone, dasatinib, dual Abl/Src inhibitor, are currently I/II clinical trials imatinib-resistant CML, very encouraging results. While most attractive target, signal transduction downstream can intercepted specific inhibitors, such as blockers farnesyl transferase mTOR. Some these compounds patients, results not yet available. Although probably capable eradicating CML stem cells, many this agent turned life-threatening into disorder does significantly affect quality life.