The role of breast cancer organ specific metastasis on the therapeutic impact of anti-cancer drugs

项目摘要 在美国，每年乳腺癌导致大约40，000名妇女死亡。 强调需要改进治疗这种疾病的选择。这项建议 重点关注晚期乳腺癌，癌细胞已经扩散， （转移），中位生存期约为3年， 诊断时间。我们将测试乳腺癌的位置是否扩散-这可以 包括肝脏，肺和大脑-改变了乳腺癌细胞对 化疗 在具体目标1中，我们将建立乳腺癌转移到不同部位的模型 然后检测对化疗药物的相对反应。在具体目标2中， 将探索宿主因素，包括宿主免疫系统细胞， 改变乳腺癌转移的扩散模式及其对 化疗我们的假设是乳腺癌转移到不同的器官 导致肿瘤细胞对抗癌剂的器官依赖性敏感性。整体 该项目将探索乳腺癌转移的位置在多大程度上 可以确定其对现有药物的敏感性。对我们假设的检验可能会导致 到更有效的治疗策略-那些适合的位置， 转移以这种方式优化治疗应该提高现有治疗的疗效。 乳腺癌患者的总体生存时间增加的治疗。

PROJECT SUMMARY Every year breast cancer causes the death of around 40,000 women in the United States, highlighting the need to improve the options to treat this disease. This proposal focuses on late stage breast cancer, where the cancer cells have spread (metastasized), and for which the median survival is approximately 3 years from the time of diagnosis. We will test whether the location of breast cancer spread – which can include the liver, the lung, and brain – alters the sensitivity of the breast cancer cells to chemotherapy. In Specific Aim 1, we will establish models of breast cancer metastases to different sites and then test the relative response to chemotherapeutic drugs. In Specific Aim 2, we will explore the extent to which host factors, including host immune system cells, can alter the pattern of dissemination of breast cancer metastases and their response to chemotherapy. Our hypothesis is that breast cancer metastasis to different organs results in organ-dependent sensitivity of the tumor cells to anti-cancer agents. Overall this project will explore the extent to which the location of a breast cancer metastasis can determine its sensitivity to available drugs. The testing of our hypothesis could lead to more effective therapeutic strategies – those that are tailored to the location of the metastases. Optimizing therapy in such a way should improve the efficacy of available therapies leading to increased overall survival time of patients with breast cancer.