Dr. Grandis’ laboratory is focused on elucidation of the key alterations that contribute to the development and progression of head and neck squamous cell carcinoma (HNSCC), with the ultimate goal of targeting these alterations for cancer therapy. She has demonstrated the prognostic role of the epidermal growth factor receptor (EGFR) and developed an innovative approach to EGFR inhibition, which is now undergoing phase II clinical evaluation. Her group has contributed to the understanding of crosstalk of signaling pathways in HNSCC where activation of selected pathways in the setting of EGFR blockade contributes to resistance to EGFR inhibitors. Clinical studies are underway that combine inhibition of EGFR with selected inhibitors of other pathways that engage in crosstalk with EGFR. They also demonstrated that Signal Transducer and Activator of Transcription 3 (STAT3) is a plausible therapeutic target and developed a novel transcription factor decoy approach to block this STAT3 signaling. A phase 0 trial was recently completed and efforts are now underway to modify the decoy to enable systemic delivery. Her group demonstrated the presence of the altered EGFR, EGFRvIII, in HNSCC where it appears to contribute to resistance to monoclonal antibody targeting of EGFR. Using a bedside-to-bench approach, they are systematically testing the pharmacodynamic effects of plausible molecular targeting agents in HNSCC subjects. Integration of genomic and pharmacodynamic data will allow for a more rational approach to select agents for use in individual cancer patients.