Globally, head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, and affects ~500,000 individuals. In the US alone, oral cancer accounts for more deaths annually than cervical cancer, melanoma, or lymphoma. The 5-year survival rate is less than 50%, a prognosis that is poorer than breast cancer or melanoma. The poor prognosis of HNSCC is due to late detection; either due to poor visualization as in the posterior-lateral tongue; or due to an innocuous red or white clinical appearance that is easily confused with inflammation or irritation. Patients with late stage HNSCC receive highly aggressive surgical and radiation treatment, leading to loss of tissues such as the tongue and salivary glands. The surviving patient must confront monumental physical and emotional challenges that include facial disfiguration, feeding and speech impediments and poor quality of life. Although, a significant proportion of late stage tumors would have responded to chemotherapy/radiation (no surgery), no predictive parameters of treatment response exist. What is needed is a high throughput screening assay for HNSCC. Development of such knowledge will enhance detection of HNSCC and improve patient survival and quality of life. Patients with cancer produce antibodies against tumor-specific antigens, suggesting that these autoantibodies may have diagnostic and prognostic value. Preliminary data here indicate that a specific antibody repertoire can be identified for HNSCC. Defining the entire antibody repertoire produced against tumor antigens in HNSCC will lead to highly specific and sensitive multiplexed assays for detection of HNSCC. Thus, the central hypothesis of the proposed research is that the endogenous immune system can be harnessed as a biological """"""""sensor"""""""" for detection of HNSCC. The objectives are to develop a HNSCC phage display library and to characterize the """"""""humoral signature"""""""" for HNSCC using phage immunomic microarrays. ? ?

Public Health Relevance

The poor prognosis of HNSCC is attributable to late detection; either due to poor visualization as in the posterior tongue; or to an innocuous red or white clinical appearance easily confused with irritation. Current oral cancer screening tests are inadequate, not specific, and poorly accessed. Patients with cancer produce antibodies against tumor-specific antigens, suggesting that these autoantibodies may have diagnostic and prognostic value. Thus, the endogenous immune system can be harnessed as a biological """"""""sensor"""""""" for early detection of HNSCC. This will be accomplished by developing a HNSCC phage display library and immunomic microarrays and using these systems to characterize the humoral signature for HNSCC. This will lead to highly specific and sensitive multiplexed assays for early detection of HNSCC. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE017977-01A2
Application #
7470452
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Shirazi, Yasaman
Project Start
2008-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
1
Fiscal Year
2008
Total Cost
$228,000
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Dentistry
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Russo, Nickole; Bellile, Emily; Murdoch-Kinch, Carol Anne et al. (2016) Cytokines in saliva increase in head and neck cancer patients after treatment. Oral Surg Oral Med Oral Pathol Oral Radiol 122:483-490.e1
Van Tubergen, Elizabeth A; Banerjee, Rajat; Liu, Min et al. (2013) Inactivation or loss of TTP promotes invasion in head and neck cancer via transcript stabilization and secretion of MMP9, MMP2, and IL-6. Clin Cancer Res 19:1169-79
Russo, N; Wang, X; Liu, M et al. (2013) A novel approach to biomarker discovery in head and neck cancer using an autoantibody signature. Oncogene 32:5026-37
Scanlon, C S; Van Tubergen, E A; Inglehart, R C et al. (2013) Biomarkers of epithelial-mesenchymal transition in squamous cell carcinoma. J Dent Res 92:114-21
Banerjee, Rajat; Russo, Nickole; Liu, Min et al. (2012) Rap1 and its regulatory proteins: the tumor suppressor, oncogene, tumor suppressor gene axis in head and neck cancer. Small GTPases 3:192-7
Palanisamy, V; Jakymiw, A; Van Tubergen, E A et al. (2012) Control of cytokine mRNA expression by RNA-binding proteins and microRNAs. J Dent Res 91:651-8
Van Tubergen, Elizabeth; Vander Broek, Robert; Lee, Julia et al. (2011) Tristetraprolin regulates interleukin-6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma. Cancer 117:2677-89
Banerjee, Rajat; Henson, Bradley S; Russo, Nickole et al. (2011) Rap1 mediates galanin receptor 2-induced proliferation and survival in squamous cell carcinoma. Cell Signal 23:1110-8