Kinase inhibitors in chronic myelogenous leukemia

Alfonso Quintás-Cardama, Jorge Cortes

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The Bcr-Abl tyrosine kinase inhibitor imatinib mesylate launched the era of molecular targeted therapy and constitutes a milestone in oncology history. However, despite impressive cytogenetic response rates achieved with this agent in patients with chronic myelogenous leukemia (CML) in chronic phase, those with advanced-stage CML frequently obtain more modest responses that are in many instances of short duration. Several mechanisms of resistance to imatinib have been described among patients that develop clinical resistance to imatinib. Point mutations in the Bcr-Abl kinase domain that impair the ability of imatinib to inhibit the kinase activity represent the leading cause of resistance. Several approaches are being pursued to overcome these mutations. In addition, many other protein kinases implicated in signaling transduction downstream Bcr-Abl play critical roles in the pathogenesis of CML, thus representing potential therapeutic targets. Multiple compounds are being screened to identify inhibitors of these kinases. This article focuses on the current state of development of new kinase inhibitors for the therapy of CML.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalClinical Advances in Hematology and Oncology
Volume4
Issue number5
StatePublished - May 1 2006
Externally publishedYes

Keywords

  • CML
  • Dasatinib
  • Nilotinib
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Hematology
  • Oncology

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