Dr. Rubin Grandis’ research program is dedicated to increasing our understanding of the genetic alterations in the upper aerodigestive tract mucosa, which result in head and neck squamous cell carcinoma. The overall goal is to identify pathways that can serve as therapeutic targets for novel preventive or treatment strategies. We are studying signaling pathways regulated by the epidermal growth factor receptor (EGFR), stimulated by direct activation (EGFR ligand) and indirect activation (G-protein-coupled receptor ligand). Cumulative evidence from our lab today suggests that EGFR autocrine signaling is activated early in head and neck carcinogenesis where expression levels of ligand or receptor are important prognostic indicators in head and neck cancer patients. Strategies aimed at blocking the ligand or receptor demonstrated anti-tumor efficacy in preclinical models and in a phase I clinical trial to investigate the toxicity and biologic effects of EGFR antisense gene therapy.
Other studies are aimed at elucidating the molecular mechanisms underlying the EGFR autocrine regulatory pathway. This work has demonstrated mitogenic signaling as a result of EGFR-mediated activation of selective STAT proteins including STAT3. Current projects are investigating strategies to block activated STAT3 including a transcription factor decoy, which has completed early phase clinical testing and a small molecule inhibitors that have emerged from a high content drug screening effort. In summary, our translation research efforts are dedicated to elucidating the critical growth pathways in head and neck cancer progression. By characterizing cell lines and patient tissues, followed by examination of mitogenic signaling mechanisms in preclinical animal models, we hope to develop innovative approaches to preventing and treating this frequently fatal malignancy.
Back to Top