凝血噁烷通路在乳腺癌肺转移中的功能及分子机制研究

作为肿瘤三级预防的重要组成部分，如何降低乳腺癌确诊患者远端转移的发生风险是临床亟待解决的重大课题。凝血噁烷是一种重要的前列腺素，其主要生理作用为促进血小板凝聚和平滑肌收缩。前期研究意外揭示：伴随乳腺癌远端肺转移的发生发展，凝血噁烷通路异常激活，但其生物学功能和作用机制至今尚未明了。本项目将主要围绕“凝血噁烷是否和如何介导乳腺癌肺转移”这一科学问题展开，拟利用临床样本分析凝血噁烷通路介导乳腺癌肺转移的可能性，借助小鼠乳腺癌自发肺转移及患者来源的移植瘤模型综合评价凝血噁烷通路作为乳腺癌肺转移防治靶标的潜力，并在细胞和分子水平阐明凝血噁烷通路介导乳腺癌肺转移的作用机制，以期为未来药物研发及乳腺癌综合防治新策略的制定提供科学依据和理论基础。

Breast cancer is the most common cancer in women worldwide. Despite decades of advances in chemotherapeutic regimens, metastasis remains to be the leading cause of breast cancer-related death. Inspired by the fact that thromboxane A2 (TXA2) pathway is constitutively activated in breast cancer metastasis, we hypothesize that platelet COX-1-derivated TXA2 might cooperate with transforming growth factor-beta 1（TGF-β1）signaling pathway to direct breast metastasis to distant organs (such as lung, liver, bone and brain) which highly express thromboxane synthase (TBXAS1). This study might establish the importance of the TXA2 pathway in breast pathophysiology, and laid the groundwork for introducing a TXA2-targeting strategy to breast metastasis prevention, early detection and management.