Single cell resolution images of a small cancer on the dorsal surface of the tongue. The image was generated using a laser scanning confocal endo-microscope and a fluorescent dye that specifically labels transformed cells. This non-invasive technology will enable this project to follow the development and experimental treatment of oral cancers with Smac-mimetic drugs in situ. A) Confocal scanning microscope probe. B) Photograph of tongue with cancer. C) Transformed cell nuclei highlighted, surrounded by auto-fluorescent lingual papillae.
Despite improvements in surgical techniques and chemoradiotherapy, 50% of patients will die from treated head and neck squamous cell cancers (HNSCC) over 5 years. Survival rates have not improved for over 30 years until recently. A new class of anti-cancer drugs, called Smac-mimetics, combined with chemoradiotherapy has been shown to double survival rates which represents a major breakthrough. However, it is not clear why only components of treatment combinations are optimal, which forms the focus of our research. Using cutting edge virtual biopsies, molecular profiling and radiation therapy in genetic mouse models of HNSCC, we will systematically define the critical ingredients to successful treatment combinations using Smac-mimetics radiation therapy, chemotherapy and immunotherapy. We will then define the best treatment to be used for molecularly defined subgroups of HNSCC to improve personalized patient treatment options and cancer survival rates.