Defining head and neck squamous cell carcinoma (HNSCC) prognostic and predictive biomarkers is anticipated to provide insights Into molecular contributors to disease progression and to contribute to HNSCC disease control. An ongoing effort by the Head and Cancer Program at the University of Pittsburgh has collected peripheral blood DNA from HNSCC cases and controls and demographic and tobacco use data beginning In 2000;tumor tissues have also been archived. Clinical, pathologic, and follow-up data continues to be collected for these 790 HNSCC cases. In addition to this large specimen and data collection, we have high-through-put genomic and proteomic technologies and expertise. We are therefore uniquely poised to evaluate biomarkers associated with HNSCC risk and prognosis. Epidermal growth factor receptor (EGFR) and gastrin-releasing peptide receptor (GRPR) are strongly implicated In HNSCC development/progression. Dr. Egloff proposes to: (1) determine whether EGFR/GRPR genetic variants are related to developing HNSCC using a case-control study;(2) determine whether EGFR/GRPR polymorphisms are prognostic indicators for HNSCC;and (3) evaluate correlations between HNSCC protein levels and EGFR/GRP R variant genotypes. These studies will be carried out with a carefully selected team of mentors and advisors who will provide expertise and guidance covering all aspects of the proposed studies. Dr. Egloff is an Assistant Professor in the Department of Otolaryngology, University of Pittsburgh with experience in translational research and formal training in cancer epidemiology and genetics. The candidate has outlined a career development plan including formal training in statistical genetics designed to facilitate her transition to an independent molecular epidemiologist cancer researcher.

Public Health Relevance

The proposed studies will test the overall hypothesis that EGFR and GRPR genetic variants contribute to HNSCC risk and disease progression and are designed to gain insights into the molecular etiology of HNSCC and to define populations at risk for developing HNSCC and/or worse disease prognosis. Results of these studies are anticipated to inform treatment decisions and contribute significantly to HNSCC disease control.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07CA137140-03
Application #
8128447
Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
Project Start
2009-09-04
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
3
Fiscal Year
2011
Total Cost
$105,126
Indirect Cost
Name
University of Pittsburgh
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Stabile, L P; Egloff, A M; Gibson, M K et al. (2017) IL6 is associated with response to dasatinib and cetuximab: Phase II clinical trial with mechanistic correlatives in cetuximab-resistant head and neck cancer. Oral Oncol 69:38-45
Li, Hua; Wheeler, Sarah; Park, Yongseok et al. (2016) Proteomic Characterization of Head and Neck Cancer Patient-Derived Xenografts. Mol Cancer Res 14:278-86
Wen, Yihui; Li, Hua; Zeng, Yan et al. (2016) MAPK1E322K mutation increases head and neck squamous cell carcinoma sensitivity to erlotinib through enhanced secretion of amphiregulin. Oncotarget 7:23300-11
Van Allen, Eliezer M; Lui, Vivian W Y; Egloff, Ann Marie et al. (2015) Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma. JAMA Oncol 1:238-44
Fung, Christopher; Zhou, Pei; Joyce, Sonali et al. (2015) Identification of epidermal growth factor receptor (EGFR) genetic variants that modify risk for head and neck squamous cell carcinoma. Cancer Lett 357:549-56
Kagawa, S; Natsuizaka, M; Whelan, K A et al. (2015) Cellular senescence checkpoint function determines differential Notch1-dependent oncogenic and tumor-suppressor activities. Oncogene 34:2347-59
Lei, Yu; Lui, Vivian W Y; Grandis, Jennifer R et al. (2014) Identification of mutations in the PYRIN-containing NLR genes (NLRP) in Head and Neck Squamous Cell Carcinoma. PLoS One 9:e85619
Egloff, Ann Marie; Lee, Ju-Whei; Langer, Corey J et al. (2014) Phase II study of cetuximab in combination with cisplatin and radiation in unresectable, locally advanced head and neck squamous cell carcinoma: Eastern cooperative oncology group trial E3303. Clin Cancer Res 20:5041-51
Egloff, Ann Marie; Liu, Xuwan; Davis, Autumn L Gaither et al. (2013) Elevated gastrin-releasing peptide receptor mRNA expression in buccal mucosa: association with head and neck squamous cell carcinoma. Head Neck 35:270-9
Wheeler, Sarah; Siwak, Doris R; Chai, Raymond et al. (2012) Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. Clin Cancer Res 18:2278-89

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