Understanding the effects of adjuvant endocrine therapy on thermoregulation

项目总结 他莫昔芬是一种雌激素样药物，用于治疗乳腺癌患者、乳腺癌幸存者和 有乳腺癌家族史的患者。作为一种治疗方法，他莫昔芬在减少 罹患癌症和提高患者存活率的变化。我们研究的目标是了解 他莫昔芬如何影响其他对雌激素敏感的组织，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，这种失调是基础 接受他莫昔芬治疗的患者潮热的产生。我们将使用尖端的分子 在下丘脑和基因工程小鼠中确定他莫昔芬敏感细胞类型的工具 鉴定介导他莫昔芬控温效应的细胞类型和受体。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。归根结底，这 信息可以用来设计治疗或佐剂，以缓解 他莫昔芬和改善乳腺癌患者和幸存者的生活质量。

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.