The non-receptor protein tyrosine kinase, focal adhesion kinase (FAK, also known as PTK2), is a key mediator of signal transduction downstream of integrins and growth factor receptors in a variety of cells, including endothelial cells. FAK is upregulated in several advance-stage solid tumors and has been described to promote tumor progression and metastasis through effects on both tumor cells and stromal cells. This has led to the development of several FAK-inhibitors, some of which have entered clinical trials (GSK2256098, VS-4718, VS-6062, VS-6063 and BI853520). Resistance to chemotherapy is a serious limitation of cancer treatment and, until recently, most studies were restricted to tumor cells, excluding the possible roles performed by the tumor microenvironment. A recent report identified endothelial cell FAK (EC-FAK) as a major regulator of chemosensitivity. By disregulating endothelial cell-derived paracrine (also known as angiocrine) signals, loss of FAK solely in the endothelial cell compartment is able to induce chemosensitisation to DNA-damaging therapies in the malignant cell compartment and thereby reduce tumor growth. Herein, we have summarized the roles of EC-FAK in cancer and development and reviewed the status of FAK-targeting anti-cancer strategies.
- Received February 9, 2016.
- Revision received May 12, 2016.
- Accepted May 13, 2016.
- Copyright ©2016, American Association for Cancer Research.