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Current Hematologic Malignancy Reports

, Volume 5, Issue 2, pp 70–80 | Cite as

Tyrosine Kinase Inhibitors: The First Decade

  • Meetu Agrawal
  • Ravin J. Garg
  • Jorge Cortes
  • Alfonso Quintás-CardamaEmail author
Article

Abstract

The treatment of chronic myeloid leukemia (CML) drastically changed with the introduction of imatinib mesylate, a Bcr-Abl1 tyrosine kinase inhibitor (TKI), in 1998. By directly targeting this leukemogenic protein kinase, imatinib affords patients with CML sustained chromosomal remissions, which translate into prolonged survival. However, there has been concern over the emergence of resistance to imatinib, and some patients fail to respond or are intolerant of imatinib therapy because of untoward toxicity. This has spurred interest in developing novel TKIs to overcome the mechanisms of resistance that lead to treatment failure—most importantly, Bcr-Abl1 kinase domain mutations. Two of these second-generation TKIs, nilotinib and dasatinib, are approved worldwide for the treatment of CML after imatinib failure or intolerance. Although these agents are active, they fail in many patients because of the development of highly resistant mutations such as the T315I, against which several novel agents are currently being tested in clinical trials. This review provides an account of the progress made in the field of TKI therapy for CML over the past decade.

Keywords

Chronic myeloid leukemia CML Tyrosine kinase inhibitors TKIs Cancer therapy Imatinib Nilotinib Dasatanib 

Notes

Disclosure

Dr. Quintás-Cardama is a speaker for Bristol-Myers Squibb and Novartis. No other potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Meetu Agrawal
    • 1
  • Ravin J. Garg
    • 1
  • Jorge Cortes
    • 1
  • Alfonso Quintás-Cardama
    • 1
    Email author
  1. 1.Department of LeukemiaUniversity of Texas MD Anderson Cancer CenterHoustonUSA

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