Targeting Pyk2 for therapeutic intervention

Expert Opin Ther Targets. 2010 Jan;14(1):95-108. doi: 10.1517/14728220903473194.


Importance of the field: The focal adhesion tyrosine kinases FAK and Pyk2 are uniquely situated to act as critical mediators for the activation of signaling pathways that regulate cell migration, proliferation and survival. By coordinating adhesion and cytoskeletal dynamics with survival and growth signaling, FAK and Pyk2 represent molecular therapeutic targets in cancer as malignant cells often exhibit defects in these processes.

Areas covered in this review: This review examines the structure and function of the focal adhesion kinase Pyk2 and intends to provide a rationale for the employment of modulating strategies that include both catalytic and extra-catalytic approaches that have been developed in the last 3 - 5 years.

What the reader will gain: Targeting tyrosine kinases in oncology has focused on the ATP binding pocket as means to inhibit catalytic activity and downregulate pathways involved in tumor invasion. This review discusses the available catalytic inhibitors and compares them to the alternative approach of targeting protein-protein interactions that regulate kinase activity.

Take home message: Development of specific catalytic inhibitors of the focal adhesion kinases has improved but significant challenges remain. Thus, approaches that inhibit the effector function of Pyk2 by targeting regulatory modules can increase specificity and will be a welcome asset to the therapeutic arena.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Catalysis
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use*
  • Focal Adhesion Kinase 2 / antagonists & inhibitors*
  • Focal Adhesion Protein-Tyrosine Kinases / antagonists & inhibitors
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Protein Conformation


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Isoenzymes
  • Focal Adhesion Kinase 2
  • Focal Adhesion Protein-Tyrosine Kinases