Targeting focal adhesion kinase signaling in tumor growth and metastasis.
BACKGROUND
Focal adhesion kinase (FAK), a crucial mediator of integrin and growth factor signaling, is a novel and promising target in cancer therapy. FAK resides within focal adhesions which are contact points between extracellular matrix (ECM) and cytoskeleton, and increased expression of the kinase has been linked with cancer cell migration, proliferation and survival. The aim of this review is to summarize the current research in the area and to assess the potential of different FAK-targeting strategies for cancer therapy.


METHODS
We briefly examine the evidence pointing towards FAK as potential anti-cancer target since its discovery in 1992. Then, we summarize different approaches developed to interfere with FAK signaling and important results reported from these experiments. Finally, we discuss the potential of these strategies to accomplish inhibition of tumor growth and distant spread as well as potentially meaningful combinations with other therapeutic modalities in the context of the currently available evidence.


RESULTS
The review emphasizes the link between FAK biology and the consequences of interference with FAK signaling. Based on this foundation an opinion is formed with regard to the future of FAK as therapeutic target.


CONCLUSIONS
Inhibition of FAK harbours the potential to restrain malignant growth and progression with minimal side effects in normal tissues. Small molecule inhibitors of the kinase should be examined in further clinical studies and combinations with existing therapies need to be explored. More efforts are required to identify markers which predict response towards FAK inhibition.
Schwock
Joerg
J
Princess Margaret Hospital/Ontario Cancer Institute (PMH/OCI), Toronto M5G 2M9, Ontario, Canada.
Dhani
Neesha
N
Hedley
David W
DW
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; D051416:Focal Adhesion Protein-Tyrosine Kinases