New Targeted Therapies for Chronic Myelogenous Leukemia: Opportunities to Overcome Imatinib Resistance

Elias Jabbour, Jorge Cortes, Susan O'Brien, Francis Giles, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

The advent of tyrosine kinase inhibitors (TKIs) has ushered in a new era in the management of chronic myelogenous leukemia (CML). Imatinib, the first TKI to be approved for the treatment of CML and the current standard first-line therapy, has significantly improved the prognosis of patients with CML. Nevertheless, a minority of patients in chronic-phase CML and even more patients with advanced-phase disease demonstrate resistance to imatinib or develop resistance during treatment. In 40% to 50% of cases, this is attributed to the development of mutations that impair the ability of imatinib to bind to and inhibit the constitutively active Bcr-Abl kinase. Consequently, researchers have developed novel, more potent TKIs that can overcome not only Bcr-Abl-dependent mechanisms of resistance, but also those that are Bcr-Abl-independent. These include: dasatinib, a potent dual Bcr-Abl and Src inhibitor; nilotinib, a selective, potent Bcr-Abl inhibitor; bosutinib (SKI-606) and INNO-406 (NS-187), which are both Src-Abl inhibitors; and others. Combination therapy is also being explored concurrently using agents that affect a variety of oncogenic pathways and immune modulation. Herein, we review some of these strategies, particularly those for which clinical data are currently available.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalSeminars in Hematology
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Leukemia, Myeloid, Chronic Phase
Disease Resistance
Therapeutics
Phosphotransferases
Research Personnel
Mutation
Imatinib Mesylate
bosutinib
bafetinib

ASJC Scopus subject areas

  • Hematology

Cite this

New Targeted Therapies for Chronic Myelogenous Leukemia : Opportunities to Overcome Imatinib Resistance. / Jabbour, Elias; Cortes, Jorge; O'Brien, Susan; Giles, Francis; Kantarjian, Hagop.

In: Seminars in Hematology, Vol. 44, No. SUPPL. 1, 01.01.2007, p. 25-31.

Research output: Contribution to journalArticle

Jabbour, Elias ; Cortes, Jorge ; O'Brien, Susan ; Giles, Francis ; Kantarjian, Hagop. / New Targeted Therapies for Chronic Myelogenous Leukemia : Opportunities to Overcome Imatinib Resistance. In: Seminars in Hematology. 2007 ; Vol. 44, No. SUPPL. 1. pp. 25-31.
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