Novel tyrosine kinase inhibitors in chronic myelogenous leukemia.

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.

• Authors: Elias Jabbour, Jorge Cortes, Hagop Kantarjian
• Journal: Current opinion in oncology (Curr Opin Oncol) Vol. 18 Issue 6 Pg. 578-83 (Nov 2006) ISSN: 1531-703X [Electronic] United States
• PMID: 16988578 (Publication Type: Journal Article, Review)

Chemical References

• Protein Kinase Inhibitors
• Protein-Tyrosine Kinases
• Fusion Proteins, bcr-abl

Topics

• Clinical Trials as Topic
• Fusion Proteins, bcr-abl (drug effects, genetics)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics, pathology)
• Protein Kinase Inhibitors (therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors)