Mechanisms of Disseminated Tumor Cell Dormancy

大多数癌症患者会死于源自播散性肿瘤的转移 细胞（DTC），治疗后数年甚至数十年。这表明DTC在休眠状态下生存， 非增殖状态然而，由于对DTC的生物学知之甚少， 机械问题，以进一步发展翻译的方法。我们的目标是确定这些机制 通过结合强大的体内模型和新的成像和纳米器件技术， 这种合作。该联盟提供了前所未有的协同作用，研究休眠和解决三个 该RFA的重点领域：1）肿瘤休眠，休眠细胞的激活和肿瘤微环境 (SAI)2）对肿瘤微环境进行成像， 肿瘤转移和休眠（SAI），以及对治疗的响应（SA 2）和3）表征 肿瘤微环境细胞外基质（ECM）的功能相关性以及肿瘤细胞如何 基质相互作用（即小生境）建立转移性细胞命运（SA 2）。我们假设至少有两个 场景影响DTC休眠。情景1：来自侵袭性癌症的DTC激活压力信号， 对诱导休眠的生长限制性靶器官微环境的反应。情景2：治疗 和/或微环境应激条件（例如缺氧）作用于携带

Majority of cancer patients will die of metastases originating from disseminated tumor cells (DTCs), years or even decades after treatment. This suggests that DTCs survive in a dormant, nonproliferative state. However, because the biology of DTCs is poorly understood it is critical to ask basic mechanistic questions to further develop translational approaches. Our goal is to identify these mechanisms by combining powerful In vivo models and novel imaging and nano-device technologies available through this collaboration. This consortium provides unprecedented synergy to study dormancy and address three emphasis areas of this RFA: 1) tumor dormancy, activation of dormant cells and the tumor microenvironment (SAI), and dormancy in response to cancer treatment (SA2); 2) imaging the tumor microenvironment during tumor metastasis, and dormancy (SAI), as well as in response to therapies (SA2) and 3) characterization and functional relevance of the tumor microenvironment extracellular matrix (ECM) and how tumor cells stroma interactions (i.e. niches) establish metastatic cell fate (SA2). We hypothesize that at least two scenarios influence DTC dormancy. Scenario 1: DTCs from invasive cancers activate stress signals in response to a growth-restrictive target organ microenvironment inducing dormancy. Scenario 2: therapy and/or microenvironmental stress conditions (e.g. hypoxia) acfing on primary tumor cells carrying a