The goals of this SPORE in Thyroid Cancer are to leverage new insights on disease pathogenesis to improve the outcome of patients with thyroid cancer at all stages of presentation. Our translational research objectives are: TR01: To explore how to implement a more rational care of patients with papillary microcarcinomas (PMC), which are highly prevalent and overtreated in the community, leading to unacceptable morbidity and wasteful health care expenditures. We propose to identify genetic predictors of progression in archival specimens and through a prospective observational study of patients with PMC left in situ, which will provide evidence-based guidelines for care. TR02: To improve the effectiveness of radioiodine (RAI) therapy in patients with RAI-refractory metastatic thyroid cancer based on new insights on the role of MAPK signaling in downregulating iodine transport and incorporation into cancer cells. TR03: To identify new approaches to treat patients with life-threatening metastatic thyroid cancer, using targeted therapies designed against key drivers of the disease, and by implementing strategies to overcome adaptive resistance mechanisms triggered by blocking key oncogenic pathways. To meet these objectives, we will undertake four main projects with the following titles: RP1: Genomic predictors of PMC disease progression. RP2: Maximizing effectiveness of radioiodine therapy by inhibiting MAPK signaling. RP3: Elucidating and targeting the molecular foundations of Hurthle cell cancer. RP4: Molecular landscape-based innovative therapies for anaplastic thyroid carcinoma. Our Developmental Research Program counts with strong candidate pilot projects, which document the robust pipeline of investigators interested in this disease, and an outstanding group of scientific advisors who will help identify and select the best projects for funding. The Career Development Program will take advantage of the strong training environment in the clinical and scientific programs at our institutions to identify and promote the research and training of young investigators focused on translational research in thyroid cancer. The SPORE will be supported by three Core facilities: CFA: Biospecimen Repository. CPB: Biostatistics. CFC: Administration.
Approximately 56,000 new patients are diagnosed with thyroid cancer in the US each year. Mortality is comparatively low but is slowly rising, and the disease continues to be a major public health challenge. The genetics of the disease make it a prime candidate for targeted therapies, which can be exploited in unique ways to improve disease outcomes.
|Ganly, Ian; Makarov, Vladimir; Deraje, Shyamprasad et al. (2018) Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes. Cancer Cell 34:256-270.e5|
|De Martino, Daniela; Yilmaz, Emrullah; Orlacchio, Arturo et al. (2018) PI3K blockage synergizes with PLK1 inhibition preventing endoreduplication and enhancing apoptosis in anaplastic thyroid cancer. Cancer Lett 439:56-65|
|Marlow, Laura A; Rohl, Stephen D; Miller, James L et al. (2018) Methodology, Criteria, and Characterization of Patient-Matched Thyroid Cell Lines and Patient-Derived Tumor Xenografts. J Clin Endocrinol Metab 103:3169-3182|
|Krishnamoorthy, Gnana P; Davidson, Natalie R; Leach, Steven D et al. (2018) EIF1AX and RAS mutations cooperate to drive thyroid tumorigenesis through ATF4 and c-MYC. Cancer Discov :|
|Untch, Brian R; Dos Anjos, Vanessa; Garcia-Rendueles, Maria E R et al. (2018) Tipifarnib Inhibits HRAS-Driven Dedifferentiated Thyroid Cancers. Cancer Res 78:4642-4657|
|Knauf, Jeffrey A; Luckett, Kathleen A; Chen, Kuen-Yuan et al. (2018) Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers. J Clin Invest 128:4086-4097|
|Xu, Bin; Tallini, Giovanni; Scognamiglio, Theresa et al. (2017) Outcome of Large Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features. Thyroid 27:512-517|
|Azouzi, Naïma; Cailloux, Jérémy; Cazarin, Juliana M et al. (2017) NADPH Oxidase NOX4 Is a Critical Mediator of BRAFV600E-Induced Downregulation of the Sodium/Iodide Symporter in Papillary Thyroid Carcinomas. Antioxid Redox Signal 26:864-877|
|Ibrahimpasic, Tihana; Xu, Bin; Landa, Iñigo et al. (2017) Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of MED12 and RBM10 as Novel Thyroid Cancer Genes Associated with Tumor Virulence. Clin Cancer Res 23:5970-5980|
|Larson, Steven M; Osborne, Joseph R; Grewal, Ravinder K et al. (2017) Redifferentiating Thyroid Cancer: Selumetinib-enhanced Radioiodine Uptake in Thyroid Cancer. Mol Imaging Radionucl Ther 26:80-86|
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