Targeting FAK to Potentiate Immune Checkpoint Therapy in Solid Tumors

The advent of immune checkpoint inhibition revolutionized cancer care, yet many people will fail to respond due to innate or acquired resistance. Combination therapies with immune checkpoint inhibitors are being explored to enhance their efficacy and improve patient outcomes. Focal adhesion kinase (FAK), known for its roles in cell adhesion and migration, has emerged as a potential therapeutic target due to the identification of its additional functions in cancer progression, including its ability to establish a pro-tumorigenic, immunosuppressive microenvironment. FAK has the ability to create physical barriers for immune cell infiltration and drug delivery through its regulation of blood vessel formation and extracellular matrix in the tumor stroma. Additionally, FAK has been reported to function both within tumor and immune cells to inhibit immune cell recruitment, stimulation, and function. Taken together, FAK functions within cancer to dampen immune surveillance and promote immune escape. As a result, there is mounting interest in the use of FAK inhibitors in combination with immune checkpoint inhibition for the treatment of solid tumors, and this strategy is actively being explored in the pre-clinical and clinical setting. This article reviews the ways in which FAK alters the tumor microenvironment and the cells within it in order to assess the clinical potential of co-targeting FAK and immune checkpoints.