SPORE in Thyroid Cancer

描述(由申请人提供)：甲状腺癌的这个孢子的目标是利用对疾病发病机制的新见解来改善甲状腺癌患者在表现的所有阶段的结果。我们的翻译研究目标是：TR01：探索如何对乳头状微癌(PMC)患者实施更合理的护理，这些患者在社区中高度流行和过度治疗，导致不可接受的发病率和医疗费用浪费。我们建议通过对留在原地的PMC患者的前瞻性观察研究，在档案标本中确定进展的遗传预测因素，这将为护理提供循证指导。TR02：基于对MAPK信号在下调碘转运和整合到癌细胞中的作用的新见解，提高放射性碘(RAI)治疗难治性转移性甲状腺癌患者的有效性。TR03：确定治疗威胁生命的转移性甲状腺癌患者的新方法，使用针对疾病关键驱动因素设计的靶向治疗，并通过实施策略来克服因阻断关键致癌途径而触发的适应性耐药机制。为了实现这些目标，我们将开展四个主要项目，标题如下：RP1：PMC疾病进展的基因组预测因素。RP2：通过抑制MAPK信号使放射性碘治疗的效果最大化。RP3：阐明并针对Hurthle细胞癌的分子基础。RP4：间变性甲状腺癌的分子景观创新疗法。我们的发展研究计划拥有强大的候选试点项目，这些项目记录了对这种疾病感兴趣的强大的研究人员队伍，以及一群杰出的科学顾问，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临床和科学计划中强大的培训环境，确定和促进专注于甲状腺癌转化性研究的年轻研究人员的研究和培训。该孢子将得到三个核心设施的支持：CFA：生物信息库。CPB：生物统计学。氟氯化碳：行政管理。

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.