UC San Diego

Key PointsFocal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that drives tumour growth and metastasis through kinase-dependent and kinase-independent pathways.FAK promotes metastasis by regulating processes involved in tumour cell motility and invasion, including control of focal adhesion and cytoskeletal dynamics, as well as the regulation of matrix metalloproteinase (MMP) surface expression.Tumour growth is enhanced through pro-proliferative and anti-apoptotic functions of FAK.FAK is connected to cancer stem cell and progenitor cell maintenance through kinase-dependent and kinase-independent functions. FAK signals contribute to the malignant outgrowth of these cells.FAK favours tumour progression via the regulation of signalling pathways within cells of the tumour microenvironment, such as endothelial cells, haematopoietic cells, platelets, macrophages and fibroblasts.FAK activity promotes endothelial cell migration, proliferation and survival, and it stimulates tumour angiogenesis. FAK-mediated regulation of endothelial cell permeability can influence tumour metastasis.FAK expression and activity in tumour and endothelial cells is frequently upregulated and correlated with a poor patient prognosis.Several molecules that target FAK kinase activity or its kinase-independent scaffolding function are under investigation in preclinical trials. Promising drug candidates in Phase I or II clinical trials are small molecule ATP-competitive inhibitors.