SPORE in Thyroid Cancer

描述（由申请人提供）：甲状腺癌孢子的目标是利用疾病发病机制的新见解来改善甲状腺癌患者在所有表现阶段的预后。我们的转化研究目标是：TR01：探讨如何对社区中高度流行和过度治疗的乳头状微癌（PMC）患者实施更合理的护理，导致不可接受的发病率和浪费的医疗保健支出。我们建议通过档案标本和对原位PMC患者的前瞻性观察研究来确定进展的遗传预测因子，这将为护理提供循证指导。TR02：基于MAPK信号在下调碘转运和进入癌细胞中的作用的新见解，提高放射性碘（RAI）治疗RAI难治性转移性甲状腺癌患者的有效性。TR03：确定治疗危及生命的转移性甲状腺癌患者的新方法，使用针对该疾病关键驱动因素的靶向治疗，并实施克服阻断关键致癌途径引发的适应性耐药机制的策略。为了实现这些目标，我们将开展以下四个主要项目：RP1: PMC疾病进展的基因组预测因子。RP2：通过抑制MAPK信号来最大化放射性碘治疗的有效性。RP3：阐明和靶向Hurthle细胞癌的分子基础。RP4：基于分子景观的甲状腺间变性癌创新疗法。我们的发展研究计划包括强有力的候选试点项目，这些项目记录了对这种疾病感兴趣的研究人员的强大渠道，以及一组杰出的科学顾问，他们将帮助确定和选择最佳的资助项目。职业发展计划将利用我们机构在临床和科学项目中强大的培训环境来确定和促进专注于甲状腺癌转化研究的年轻研究人员的研究和培训。孢子将由三个核心设施提供支持：CFA：生物标本库。心脏:生物统计学。氯氟化碳:管理。

DESCRIPTION (provided by applicant): 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.