3 OVERALL CRITIQUE 3 SPORE PROGRAM ORGANIZATION AND CAPABILITIES 6 SCIENTIFIC COLLABORATIONS 8 PROTECTION OF HUMAN SUBJECTS 10 VERTEBRATE ANIMALS 10 SCIENTIFIC REVIEW OFFICER'S NOTES 10 INDIVIDUAL PROJECTS AND CORES 11 PROJECT 1: Low-Penetrance Genes in the Predispositon to Papillary Thyroid Cancer 11 PROJECT 2: Preserving Salivary Gland Function after Radioiodine Therapy for Thyroid Cancer 15 PROJECT 3: Developing Combination Therapies for Medullary Thyroid Cancer 23 PROJECT 4: Development and Validation of Novel Circulating Medullary Thyroid Cancer Markers 29 CORE A/1: Integrated Clinicopathology and Biorespository Core 34 CORE B/2: Biostatistics Core 38 CORE C/3: Administrative Core 41 DEVELOPMENTAL RESEARCH PROGRAM 43 CAREER DEVELOPMENT PROGRAM 45 COMMITTEE BUDGET RECOMMENDATIONS 48 SPECIAL EMPHASIS PANEL ROSTER DESCRIPTION (provided by applicant): The primary goal of The Ohio State University / M.D. Anderson Thyroid Cancer SPORE 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, developing new approaches to minimize side effects of treatments, and developing better biomarkers and treatment options for progressive metastatic disease. 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 and worldwide;it s now the 5th most common malignancy in women and 11th most common in men. 2) Thyroid cancer typically takes an indolent course, thus with the increasing incidence there is an ever enlarging population of individuals (-500,000) surviving long term, many of whom suffer from lifelong effects of initial therapy. 3) For patients with more aggressive forms of thyroid cancer, such as medullary cancer (MTC), there exist no curative therapies or biomarkers that accurately predict outcome from disease or response to particular treatments thereby limiting efforts to individualize therapeutic intensity. In order to achieve our goals, this SPORE application proposes to support a multi-institutional team of experienced investigators from two of the leading institutions in the field with a history of collaborative clinical trials. We have chosen t focus on critical areas of need for rapid translation into clinical practice for thyroid cancer patients with the following four Projects supported by outstanding Cores: 1) Low-penetrance genes in the predisposition to papillary thyroid carcinoma;2) Biomarker discovery and personalized intervention of radioiodine induced salivary gland damage in thyroid cancer patients;3) Developing combination therapies for Medullary Thyroid Cancer;and 4) Development and validation of novel circulating medullary thyroid cancer markers. Through these translational Projects, as well as Career Developmental and Developmental Research Programs, we aim to impact on critical areas of need in thyroid cancer clinical management for all forms of thyroid cancer.
Thyroid cancer incidence is rising. Key issues in clinical care related to predictive testing for more aggressive disease, improving survivorship as many patients live for decades after their diagnosis, improving treatment for patients with aggressive forms of thyroid cancer and improving detection and monitoring of metastases This SPORE addresses these critical areas to improve the outcomes of patients with thyroid cancer.
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|Danysh, Brian P; Rieger, Erin Y; Sinha, Deepankar K et al. (2016) Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model. Oncotarget 7:30907-23|
|Nagy, Rebecca; Ringel, Matthew D (2015) Genetic predisposition for nonmedullary thyroid cancer. Horm Cancer 6:13-20|
|Tomsic, Jerneja; He, Huiling; de la Chapelle, Albert (2015) HABP2 Mutation and Nonmedullary Thyroid Cancer. N Engl J Med 373:2086|
|He, Huiling; Li, Wei; Liyanarachchi, Sandya et al. (2015) Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer. Proc Natl Acad Sci U S A 112:6128-33|
|He, Huiling; Li, Wei; Liyanarachchi, Sandya et al. (2015) Genetic predisposition to papillary thyroid carcinoma: involvement of FOXE1, TSHR, and a novel lincRNA gene, PTCSC2. J Clin Endocrinol Metab 100:E164-72|
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