FAK Inhibition Program

Expression of focal adhesion kinase (FAK) is greater in many tumor types as compared to normal tissue, particularly in cancers that have high invasive and metastatic capability. FAK has many kinase-dependent functions, including control of cell movement, invasion, survival and gene expression. Research at Verastem, and with our collaborators, has further advanced the understanding of the effects of FAK inhibition and has elucidated the ability of FAK kinase inhibition to overcome three key drug resistance mechanisms in the tumor microenvironment:

Cancer stem cells (CSCs)

can evade both current therapies and the immune system to mediate recurrence and metastasis. FAK is essential for both the survival and tumor-initiating capability of CSCs.1

Dense stroma

(fibroblasts and extracellular matrix) in which a tumor’s growth may prevent effective immune cell infiltration as well as potentially limiting penetration of cancer therapies. FAK inhibition decreases components of tumor-protective stroma.2, 3

Tumor evasion of the body’s adaptive immune system

can occur through evasion of immune checkpoints, including PD-1 and CTLA-4 signaling, as well as by imbalance in the levels of cytotoxic and immunosuppressive immune cells. FAK inhibition can improve the immune balance in the tumor microenvironment resulting in an improvement in the efficacy of immune checkpoint inhibitors. This includes increasing the cytotoxic T cells while decreasing the key immuno-suppressive cell types.3,4