Tyrosine kinase inhibitors: The first decade

Meetu Agrawal, Ravin J. Garg, Jorge Cortes, Alfonso Quintás-Cardama

Research output: Contribution to journalReview article

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalCurrent Hematologic Malignancy Reports
Volume5
Issue number2
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Tyrosine kinase inhibitors: The first decade'. Together they form a unique fingerprint.

  • Cite this