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  • Title: Novel tyrosine kinase inhibitors in chronic myelogenous leukemia.
    Author: Jabbour E, Cortes J, Kantarjian H.
    Journal: Curr Opin Oncol; 2006 Nov; 18(6):578-83. PubMed ID: 16988578.
    Abstract:
    PURPOSE OF REVIEW: The successful introduction of the tyrosine kinase inhibitors has initiated a new era in the management of chronic myeloid leukemia. RECENT FINDINGS: Imatinib therapy has significantly improved prognosis of chronic myeloid leukemia. A minority of patients with chronic-phase disease (4% annually) and considerably more in advanced stages develop resistance. This is attributed, in 40-50% of cases, to the development of BCR-ABL (breakpoint cluster region/Abelson oncogene) tyrosine kinase domain mutations that impair imatinib binding. This has led to the development of more potent novel tyrosine kinase inhibitors that can overcome both BCR-ABL-dependent and BCR-ABL-independent mechanisms of resistance. Preliminary results of phase I and II trials with dasatinib and nilotinib have provided promising data that may reduce disease progression and potentially prevent acquired resistance to the tyrosine kinase inhibitors. SUMMARY: Novel tyrosine kinase inhibitors with more potent and selective Bcr-Abl inhibition and with multitargeted inhibition of Bcr-Abl and Src family kinases are promising and may further improve prognosis in chronic myeloid leukemia.
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