Focal adhesion kinase-An emerging viable target in cancer and development of focal adhesion kinase inhibitors.

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase located at the extracellular matrix cell adhesion site. This kinase mediates downstream signalling cascades on the cell-extracellular matrix of integrins, cytokine receptors, growth factor receptors and G-protein-coupled receptors. Several studies have suggested the importance of FAK in cancer cell adhesion, motility, proliferation and survival and is over-expressed in cancer cells. There is a growing body of evidence indicating involvement of FAK-mediated signalling and functions in development of tumour cells, making FAK an emerging viable therapeutic target. There is substantial research impetus on development of small molecule FAK inhibitors that impact and inhibit the downstream pathways of FAK, subsequently modulating cancer progression and survival. A variety of scaffolds including hybrid scaffolds have been designed and synthesized with some translating into clinical trials. In addition to the reduction of metastasis and angiogenesis, these inhibitors are effective in inducing tumour cell apoptosis. In this paper, we provide an overview of FAK and analysis of design, synthesis and structure-activity relationship of small molecule FAK inhibitors reported till date. We have discussed FAK inhibitors in clinical trials and highlighted future prospects in the development of FAK inhibitors to augment the armamentarium of cancer therapeutics.