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


    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
    Issue number16
    StatePublished - Nov 1 2006



    • 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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