FAK in cancer: mechanistic findings and clinical applications

Focal adhesion kinase (FAK) can promote tumour growth and metastasis through various kinase-dependent and kinase-independent pathways. This Review discusses the roles of FAK in tumour cells and cells of the microenvironment, as well as the progress that is being made in the clinical development of FAK inhibitors. Focal adhesion kinase (FAK) is a cytoplasmic protein tyrosine kinase that is overexpressed and activated in several advanced-stage solid cancers. FAK promotes tumour progression and metastasis through effects on cancer cells, as well as stromal cells of the tumour microenvironment. The kinase-dependent and kinase-independent functions of FAK control cell movement, invasion, survival, gene expression and cancer stem cell self-renewal. Small molecule FAK inhibitors decrease tumour growth and metastasis in several preclinical models and have initial clinical activity in patients with limited adverse events. In this Review, we discuss FAK signalling effects on both tumour and stromal cell biology that provide rationale and support for future therapeutic opportunities.