Understanding the effects of adjuvant endocrine therapy on thermoregulation

项目摘要 他莫昔芬是一种雌激素样药物，用于治疗乳腺癌患者，乳腺癌幸存者， 有乳腺癌家族史的患者。作为一种治疗，他莫昔芬是非常有效的减少 癌症的发生和病人存活率的提高。我们研究的目的是了解 他莫昔芬如何影响其他雌激素敏感组织，特别是下丘脑。我们假设 他莫昔芬改变了下丘脑的雌激素受体信号，这种失调是 在接受他莫昔芬治疗的患者中产生潮热。我们将使用尖端的分子技术 定义下丘脑和基因工程小鼠中他莫昔芬敏感细胞类型的工具 以确定介导他莫昔芬对温度控制作用的细胞类型和受体。这 信息将帮助我们更好地了解他莫昔芬治疗如何影响大脑。最终这 这些信息可用于设计治疗或辅助剂，以减轻药物的副作用。 并改善乳腺癌患者和幸存者生活质量。

PROJECT SUMMARY Tamoxifen is an estrogen-like drug that is used to treat breast cancer patients, breast cancer survivors, and patients with a family history of breast cancer. As a treatment, tamoxifen is extremely effective at decreasing the changes of getting cancer and increasing patient survival. The goal of our research is to understand how tamoxifen may affect other estrogen-sensitive tissues, specifically the hypothalamus. We hypothesize that tamoxifen alters estrogen receptor signaling in the hypothalamus and that this dysregulation underlies the generation of hot flashes in patients undergoing tamoxifen therapy. We will use cutting-edge molecular tools to define the tamoxifen-sensitive cell types within the hypothalamus and genetically engineered mice to identify the cell types and receptors that mediate the effects of tamoxifen on temperature control. This information will help us better understand how tamoxifen therapy impacts the brain. Ultimately, this information could be used to design treatments or adjuvants that provide relief from the side effects of tamoxifen and improve quality of life for breast cancer patients and survivors.