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 and kinase-independent functions, including control of cell movement, invasion, survival, and gene expression. Research at Verastem has further advanced the understanding of the effects of FAK inhibition and now recognize its ability to overcome three key challenges in the tumor microenvironment:

  1. Cancer stem cells (CSCs) can evade both current therapies and the immune system to cause recurrence and metastasis. FAK is essential for both the survival & tumor-initiating capability of CSCs.1
  2. Dense stroma in which a tumor grows may prevent effective immune cell infiltration and cytokine signaling as well as potentially limiting penetration of cancer therapies. FAK inhibition decreases components of tumor-protective stroma.2, 3
  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 to improve upon the efficacy of immune checkpoint inhibitors. This includes increasing the cytotoxic T cells while decreasing the key immuno-suppressive cell types.3,4


[1] Kolev VN et al. FAK inhibition targets cancer stem cells. EORTC 2015
[2] Serrels et al. Nuclear FAK controls chemokine transcription, Tregs, and evasion of anti-tumor immunity. Cell. 2015
[3] Jiang et al. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nature Medicine. 2016
[4] Stokes JB et al. Inhibition of Focal adhesion Kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011