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.
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.
|Pai, Sara I; Jack Lee, J; Carey, Thomas E et al. (2018) HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers. Oral Oncol 77:92-97|
|Bishop, Justin A; Rooper, Lisa M; Chiosea, Simion I et al. (2018) Clear Cell Carcinoma of Salivary Glands Is Frequently p16 Positive: A Pitfall in the Interpretation of Oropharyngeal Biopsies. Am J Surg Pathol 42:367-371|
|Afsari, Bahman; Guo, Theresa; Considine, Michael et al. (2018) Splice Expression Variation Analysis (SEVA) for inter-tumor heterogeneity of gene isoform usage in cancer. Bioinformatics 34:1859-1867|
|Bishop, Justin A; Cowan, Morgan L; Shum, Chung H et al. (2018) MAML2 Rearrangements in Variant Forms of Mucoepidermoid Carcinoma: Ancillary Diagnostic Testing for the Ciliated and Warthin-like Variants. Am J Surg Pathol 42:130-136|
|Kelley, Dylan Z; Flam, Emily L; Guo, Theresa et al. (2018) Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma. Transl Res 202:109-119|
|Ghantous, Yasmine; Schussel, Juliana L; Brait, Mariana (2018) Tobacco and alcohol-induced epigenetic changes in oral carcinoma. Curr Opin Oncol 30:152-158|
|Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit et al. (2018) Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma. Cancer 124:84-94|
|Kagohara, Luciane T; Stein-O'Brien, Genevieve L; Kelley, Dylan et al. (2018) Epigenetic regulation of gene expression in cancer: techniques, resources and analysis. Brief Funct Genomics 17:49-63|
|Windon, Melina J; D'Souza, Gypsyamber; Rettig, Eleni M et al. (2018) Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults. Cancer 124:2993-2999|
|Ravi, Rajani; Noonan, Kimberly A; Pham, Vui et al. (2018) Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGF? enhance the efficacy of cancer immunotherapy. Nat Commun 9:741|
Showing the most recent 10 out of 137 publications