FAK as a Target for Therapy in Head and Neck Cancer

Despite decades of concerted effort, treatments for head and neck squamous cell carcinoma (HNSCC) have remained largely unchanged, with tumors typically managed using a combination of surgery, radiotherapy, and cytotoxic chemotherapy. Suboptimal efficacy and often severe toxicities associated with some of these treatments have encouraged development of targeted therapies that may overcome these limitations. One promising avenue of therapeutic development in HNSCC in particular has addressed integrins and integrin-mediated signaling, which mediates interactions between the tumor and the extracellular matrix (ECM) and can potentially be targeted by inhibition of the integrin-associated focal adhesion kinase (FAK). This chapter summarizes FAK structure-function relationships and how FAK impacts multiple cellular processes relevant to HNSCC, including survival and invasion. We will discuss the development of targeted FAK inhibitors, and combinatorial strategies incorporating FAK inhibition, with comparisons between human papillomavirus (HPV)-positive and HPV-negative HNSCC.