Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

F. J. Giles, M. O'Dwyer, Ronan T Swords

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML), offering patients several targeted therapeutic options that provide the possibility of sustained remissions and prolonged survival. With the availability of imatinib, nilotinib and dasatinib, physicians must weigh the efficacy and safety profile of each agent when choosing the best therapeutic option for individual patients. Each agent targets tyrosine kinases within the cell uniquely to cause the desired antiproliferative effect. In addition to inhibiting the BCR-ABL kinase, imatinib and nilotinib target the same array of other tyrosine kinases, including c-KIT and platelet-derived growth factor receptor (PDGFR), albeit with differing potencies. While targeting BCR-ABL with the highest potency among approved agents in CML, dasatinib also targets a broad array of off-target kinases, including SRC family members, PDGFR and EPHB4. The differences in kinase inhibition profiles among these agents in vitro probably account for the differing clinical safety profiles of these agents. This paper reviews the various kinases inhibited by imatinib, nilotinib and dasatinib, and describes the potential impact of kinase inhibition on the efficacy and safety of each agent.

Original languageEnglish
Pages (from-to)1698-1707
Number of pages10
JournalLeukemia
Volume23
Issue number10
DOIs
StatePublished - Jun 5 2009
Externally publishedYes

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Phosphotransferases
Platelet-Derived Growth Factor Receptors
Safety
Therapeutics
Physicians
Survival
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Dasatinib
Inhibition (Psychology)

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. / Giles, F. J.; O'Dwyer, M.; Swords, Ronan T.

In: Leukemia, Vol. 23, No. 10, 05.06.2009, p. 1698-1707.

Research output: Contribution to journalArticle

Giles, F. J. ; O'Dwyer, M. ; Swords, Ronan T. / Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. In: Leukemia. 2009 ; Vol. 23, No. 10. pp. 1698-1707.
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