Point mutations of protein kinases and individualised cancer therapy

Michael Davies, Bryan Hennessy, Gordon B. Mills

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

The treatment of cancer is rapidly changing, with an increasing focus on converting our improved understanding of the molecular basis of disease into clinical benefit for patients. Protein kinases that are mutated in cancer represent attractive targets, as they may result in cellular dependency on the mutant kinase or its associated pathway for survival, a condition known as 'oncogene addiction'. Early clinical experiences have demonstrated dramatic clinical benefit of targeting oncogenic mutations in diseases that have been largely resistant to traditional cytotoxic chemotherapy. Further, mutational activation of kinases can indicate which patients are likely to respond to targeted therapeutics. However, these experiences have also illuminated a number of critical challenges that will have to be addressed in the development of effective drugs across different cancers, to fully realise the potential of individualised molecular therapy. This review utilises examples of genetic activation of kinases to illustrate many of the lessons learned, as well as those yet to be implemented.

Original languageEnglish (US)
Pages (from-to)2243-2261
Number of pages19
JournalExpert Opinion on Pharmacotherapy
Volume7
Issue number16
DOIs
StatePublished - Nov 1 2006
Externally publishedYes

Keywords

  • Acute myelogenous leukaemia
  • EGFR
  • Erlotinib
  • Flt-3
  • Gastrointestinal stromal tumour
  • Gefitinib
  • High-throughput DNA sequencing
  • Imatinib mesilate
  • Jak-2
  • Myeloproliferative disorders
  • PIK3CA
  • Platelet-derived growth factor receptor-α
  • b-Raf
  • c-Kit

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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