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Analytical and Bioanalytical Chemistry

, Volume 397, Issue 8, pp 3163–3171 | Cite as

Strategies for kinome profiling in cancer and potential clinical applications: chemical proteomics and array-based methods

  • Sander R. Piersma
  • Mariette Labots
  • Henk M. W. Verheul
  • Connie R. JiménezEmail author
Trends

Abstract

Kinases are key enzymes involved in deregulated signal transduction associated with cancer development and progression. The advent of personalized medicine drives the development of new diagnostic tools for patient stratification and therapy selection Ginsburg and Willard (Transl Res 154:277-287, 2009). Since deregulation of kinase-mediated signal transduction is implied in tumorigenesis, the analysis of all kinases (the kinome) active in a particular tumor may yield tumor-specific information on aberrant cell signalling pathways. Tumor tissue kinase activity profiles may correlate with response to therapy and therefore may be used for future therapy selection. In this Trend paper we describe peptide array and mass spectrometry-based technologies and new developments for kinome profiling, and we present an outlook towards future implementation of therapy selection based on kinome profiling in clinical practice.

Figure

Protein kinases and interacting proteins are enriched by immobilized kinase inhibitor affinity capture, and their identity and phosphorylation sites are identified by mass spectrometry. Kinases that are differential between responders to therapy and non-responders can be used to design custom peptide substrate arrays to detect kinase-mediated aberrant signalling in cancer tissues. These custom peptide substrate arrays can be used, when validated, for therapy selection in the clinic.

Keywords

Kinase Kinome profiling Chemical proteomics Peptide substrate array Kinase inhibitor 

Notes

Acknowledgments

This work was supported by the VUmc-Cancer Center Amsterdam (CRJ). The Aegon Foundation is acknowledged for financial support (ML).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sander R. Piersma
    • 1
  • Mariette Labots
    • 2
  • Henk M. W. Verheul
    • 2
  • Connie R. Jiménez
    • 1
    Email author
  1. 1.Department of Medical Oncology, OncoProteomics LaboratoryVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Medical Oncology, Angiogenesis LaboratoryVU University Medical CenterAmsterdamThe Netherlands

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