More than half a million new cases of head and neck squamous cell carcinoma (HNSCC) will occur in 2011, including 50,000 cases in the United States, making it the sixth most common cancer in the worid. These cancers are frequentiy lethal, with a five-year survival of only ~50%. Our group found that HNSCC is characterized by tumor suppressor gene predominance. This distinction is critical because the new generation of moleculariy-targeted therapies is directed toward activated oncogenes but such drugs cannot directly target mutated tumor suppressor genes because they are already inactivated. Given the lack of targeted therapies that are available for HNSCC, eariy detection, monitoring, and surveillance will be critical to decrease the morbidity and mortality associated with HNSCC. The ultimate goal ofthis proposal is to develop clinically useful biomarkers that can be used for early detection, monitoring, surveillance, and prognosis. To achieve this goal, we propose a detailed genetic analysis of HNSCC (AIM #1). These genetic changes will be used to develop and validate circulating tumor DNA based biomarker assay in HNSCC (Aim #2). The biomarkers will be con-elated with clinical findings and outcomes in a prospective study (Aim #3). The above studies will identify genetic changes in HNSCC and allow the development of clinically useful biomarkers.

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HNSCC is driven by mutations in tumor suppressor genes, precluding the use of targeted therapies. Eariy detection, monitoring disease burden during treatment to confirm efficacy of surgery, radiotherapy and/or chemotherapy, and surveillance for eariy detection of persistent or recurrent disease are the optimal approaches for reducing morisidity and mortality from this disease.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
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Special Emphasis Panel (ZCA1-RPRB-7)
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Johns Hopkins University
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Li, Ryan; Faden, Daniel L; Fakhry, Carole et al. (2015) Clinical, genomic, and metagenomic characterization of oral tongue squamous cell carcinoma in patients who do not smoke. Head Neck 37:1642-9
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