Protein Tyrosine Kinases as Targets for Cancer and Other Indications

  • Mark Pearson
  • Carlos García-Echeverría
  • Doriano Fabbro
Part of the Cancer Drug Discovery and Development book series (CDD&D)


The identification and characterization of the members of individual signal transduction cascades, and advances in understanding how these signals are integrated in normal and pathological conditions have provided new strategies for therapeutic intervention. Rapid progress has occurred in last few years in the development of inhibitors that target protein tyrosine kinases (PTKs), enzymes that transfer the γ-phosphate group of adenosine triphosphate (ATP) to the hydroxyl group of tyrosine residues on target proteins. Although PTKs represent a small percentage of the total number of kinases in the “kinome,” 90 of 518, a disproportional number of inhibitors currently in clinical trials are directed against them; e.g., more than 20 different tyrosine kinases are being evaluated as potential targets in oncology. There are a number of reasons why tyrosine kinases have been considered to be good targets. Epistatically, PTKs are located upstream and downstream of tumor suppressor genes or oncogenes and have been demonstrated to play central roles in apoptosis, proliferation, invasion, and differentiation (1). Aberrant activation of tyrosine kinases, owing to mutation or overexpression, is sufficient for them to become transforming in cellular and animal models. The majority of targets are receptor protein tyrosine kinases (RPTKs), as deregulating mutations of over half of the known RPTKs have been associated with different human malignancies; see Table 1 for examples. Finally, and equally as important as the epidemiological and biochemical data, the prevalence of PTKs as targets is because of the fact that they are considered druggable.


Vascular Endothelial Growth Factor Epidermal Growth Factor Receptor Tyrosine Kinase Chronic Myeloid Leukemia Protein Tyrosine Kinase 
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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Mark Pearson
    • 1
  • Carlos García-Echeverría
    • 2
  • Doriano Fabbro
    • 3
  1. 1.Oncology In Vitro Profiling (IVP)Novartis Institutes for BioMedical Research Basel, Novartis Pharma AGBaselSwitzerland
  2. 2.Global Discovery Chemistry-OncologyNovartis Institutes for BioMedical Research Basel, Novartis Pharma AGBaselSwitzerland
  3. 3.Novartis Institutes for BioMedical Research Basel, Novartis Pharma AGBaselSwitzerland

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