The incidence of thyroid cancer is rising at the second fastest rate of all malignancies in the United States and has an increasing tumor-specific mortality annually, making it an important public health problem. The reasons for this increasing incidence and rising death rate are uncertain. The goal of the P01 application is to address the key issues relating to thyroid cancer predisposition, tumorigenesis, and progression in order to enhance the potential for both early diagnosis and the effective treatment of progressive disease. Based on extensive preliminary data from our group, we propose to: (1) examine and identify predisposing genes for papillary thyroid cancer, (2) determine the critical changes responsible for the development of follicular thyroid cancer in an inherited form of the disease, Cowden syndrome, using a novel animal model, and translate this into a scheme to enhance preoperative diagnosis of this form of thyroid cancer, (3) evaluate and identify the key mechanisms of thyroid cancer induction and dedifferentiation induced by the RET/PTC 1 oncogene, one of the most common genetic abnormalities in papillary thyroid cancer, using a second novel animal model system, and (4) determine key pathways involved in tumor invasion and motility for both follicular and papillary thyroid cancers focusing on the models developed in this P01, and then test novel agents directed at blocking these pathway in vitro and in vivo. Over the past six years, the PI's of the individual projects, and the leaders of the cores have created an environment to successfully perform this integrated P01 that is unique for thyroid cancer. This includes a substantial database, integration with pathology, and a record of successful collaborative genetics, laboratory, drug development, and clinical research as evidenced by approximately thirty co-authored publications. Thus, this P01 represents an integrated Bedside-to-Bench-to-Bedside approach targeting the key clinical issues confronting the diagnosis and management of patients with thyroid cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA124570-05
Application #
8234155
Study Section
Special Emphasis Panel (ZCA1-GRB-S (O1))
Program Officer
Snyderwine, Elizabeth G
Project Start
2008-03-01
Project End
2013-04-29
Budget Start
2012-03-01
Budget End
2013-04-29
Support Year
5
Fiscal Year
2012
Total Cost
$2,209,222
Indirect Cost
$631,944
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Nabhan, Fadi; Ringel, Matthew D (2016) Thyroid nodules and cancer management guidelines: comparisons and controversies. Endocr Relat Cancer :
Shirley, Lawrence A; McCarty, Samantha; Yang, Ming-Chen et al. (2016) Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target. Surgery 159:163-70
Tomsic, Jerneja; Fultz, Rebecca; Liyanarachchi, Sandya et al. (2016) HABP2 G534E Variant in Papillary Thyroid Carcinoma. PLoS One 11:e0146315
Harshman, Sean W; Canella, Alessandro; Ciarlariello, Paul D et al. (2016) Proteomic characterization of circulating extracellular vesicles identifies novel serum myeloma associated markers. J Proteomics 136:89-98
Kirschner, Lawrence S; Qamri, Zahida; Kari, Suresh et al. (2016) Mouse models of thyroid cancer: A 2015 update. Mol Cell Endocrinol 421:18-27
Justiniano, Steven E; McElroy, Joseph P; Yu, Lianbo et al. (2016) Genetic variants in thyroid cancer distant metastases. Endocr Relat Cancer 23:L33-6
Wang, Yanqiang; Li, Wei; Phay, John E et al. (2016) Primary Cell Culture Systems for Human Thyroid Studies. Thyroid 26:1131-40
Nagy, Rebecca; Ringel, Matthew D (2015) Genetic predisposition for nonmedullary thyroid cancer. Horm Cancer 6:13-20
Yehia, Lamis; Niazi, Farshad; Ni, Ying et al. (2015) Germline Heterozygous Variants in SEC23B Are Associated with Cowden Syndrome and Enriched in Apparently Sporadic Thyroid Cancer. Am J Hum Genet 97:661-76
Tomsic, Jerneja; He, Huiling; de la Chapelle, Albert (2015) HABP2 Mutation and Nonmedullary Thyroid Cancer. N Engl J Med 373:2086

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