Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide, with high morbidity, high mortality, and few therapeutic options outside of surgery, standard cytotoxic chemotherapy, and radiation. Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of HNSCC and is associated with poor outcome. An EGFR monoclonal antibody, cetuximab, is the only FDA-approved cancer intrinsic molecular targeted therapy for HNSCC; however, resistance eventually occurs in all patients. In my graduate studies, functional screens, including a small-molecule kinase inhibitor screen and siRNA screening panels, were used to identify agents that synergized with EGFR inhibitors in reducing viability in HNSCC patient-derived tumor cells. Bioinformatics analysis was performed to determine the coverage by the drugs on the inhibitor assay of genomic alterations in the HNSCC The Cancer Genome Atlas (TCGA) cohort.