Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics

Abstract

Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer.

Fig. 1. Components of the FAK scaffold that promote tumor cell survival

FAK interacts with many oncogenic tyrosine kinases, tumor suppressor genes, and tumor-related proteins across its broad N- and C-terminal domains.

Fig. 2. Advantages of targeting the FAK scaffold in cancer cells versus normal cells

Inhibitors that target the FAK scaffold have the potential to specifically target oncogenic-related proteins and reactivate tumor-suppressing proteins in cancer cells while sparing normal cell counterparts that do not rely on these signals for survival.