The primary goal of this P01 is to improve the outcomes and lives of patients with thyroid cancer by identifying genetically """"""""at-risk"""""""" individuals allowing for early diagnosis and prediction of tumor behavior, new pathways that influence cancer development and progression, and improving outcomes of patients with metastatic disease by improving existing therapies or validating new treatment targets. Several factors support the importance of applying these efforts to thyroid cancer: (1) Thyroid cancer incidence is rising at the fastest rate of all malignancies in the United States. (2) Thyroid cancer typical takes an indolent course when patients are diagnosed early, thus with the increasing incidence there is an ever enlarging population of individuals surviving long-term. (3) For patients with more aggressive forms of thyroid cancer, current treatment options need to be improved or replaced with more effective treatments. Over the course of the first cycle of this P01 our group has together worked toward these goals and made key observations with potential to impact on patients with differentiated thyroid cancer (papillary and follicular). The goal for this competing renewal is to extend the work on the most promising findings that have greatest likelihood to be translated into practice or that represent key advances in the field with potential to alter paradigms used in research or clinical practice. Specifically, we will functionally characterize genes that predispose to PTC in families identified in the first cycle of the P01 and apply new technologies to a larger number of informative families to identify more potential genes that predispose to PTC (Project 1), extend the work using a candidate gene approach for FTC and PTC risk that has identified interactions between signaling pathways (Project 2);design approaches to enhance 1-131 therapy using novel mouse imaging techniques developed in the P01 and extend that work to identify other unknown regulators of this process (Project 3);and fully determine the role and potential therapeutic importance of p21 activated kinase (PAK), a newly identified signaling pathway downstream of BRAF, in thyroid cancer in vivo, and determine its role in resistance to RAF inhibitors (Project 4).

Public Health Relevance

Thyroid cancer incidence is rising. Key issues in clinical care relate to defining the risk of developing thyroid cancer, identifying key pathways involve in tumor formation or predisposition, developing methods to improve existing treatments, and defining pathways involved in disease progression to develop new therapies. This P01 addresses these critical areas to improve the outcomes of patients with thyroid cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-O (J1))
Program Officer
Yassin, Rihab R,
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Ohio State University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Saporito, Donika; Brock, Pamela; Hampel, Heather et al. (2018) Penetrance of a rare familial mutation predisposing to papillary thyroid cancer. Fam Cancer 17:431-434
Segkos, Konstantinos; Porter, Kyle; Senter, Leigha et al. (2018) Neck Ultrasound in Patients with Follicular Thyroid Carcinoma. Horm Cancer 9:433-439
Kotlarek, Marta; Kubiak, Anna; Czetwerty?ska, Ma?gorzata et al. (2018) The rs2910164 Genetic Variant of miR-146a-3p Is Associated with Increased Overall Mortality in Patients with Follicular Variant Papillary Thyroid Carcinoma. Int J Mol Sci 19:
Russart, Kathryn L G; Huk, Danielle; Nelson, Randy J et al. (2018) Elevated aggressive behavior in male mice with thyroid-specific Prkar1a and global Epac1 gene deletion. Horm Behav 98:121-129
Ashtekar, Amruta; Huk, Danielle; Magner, Alexa et al. (2018) Alterations in Sod2-Induced Oxidative Stress Affect Endocrine Cancer Progression. J Clin Endocrinol Metab 103:4135-4145
Smith, Iris Nira; Thacker, Stetson; Jaini, Ritika et al. (2018) Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes. J Biomol Struct Dyn :1-17
Feng, Fang; Yehia, Lamis; Ni, Ying et al. (2018) A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling. Cancer Res 78:6121-6133
Byrd, Victoria; Getz, Ted; Padmanabhan, Roshan et al. (2018) The microbiome in PTEN hamartoma tumor syndrome. Endocr Relat Cancer 25:233-243
Yehia, Lamis; Jindal, Supriya; Komar, Anton A et al. (2018) Non-canonical role of cancer-associated mutant SEC23B in the ribosome biogenesis pathway. Hum Mol Genet 27:3154-3164
Chakedis, Jeffery; Shirley, Lawrence A; Terando, Alicia M et al. (2018) Identification of the Thoracic Duct Using Indocyanine Green During Cervical Lymphadenectomy. Ann Surg Oncol 25:3711-3717

Showing the most recent 10 out of 131 publications