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(DCs)，治疗后数年甚至数十年。这表明DTC在休眠状态下存活， 非增殖状态。然而，由于对DTC的生物学了解甚少，因此询问BASIC是至关重要的 进一步发展翻译方法的机械性问题。我们的目标是确定这些机制 通过将强大的活体模型与新的成像和纳米设备技术相结合， 这种合作。该联盟为研究休眠和解决三个问题提供了前所未有的协同作用 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)，和对癌症治疗的休眠(SA2)；2)成像肿瘤微环境 肿瘤转移、休眠(SAI)以及对治疗的反应(SA2)和3)特征 肿瘤微环境细胞外基质(ECM)与肿瘤细胞功能的相关性 间质相互作用(即小生境)决定转移细胞的命运(SA2)。我们假设至少有两个 场景会影响DTC休眠。情景1：来自浸润性癌症的DTC激活应激信号 对限制生长的目标器官微环境诱导休眠的反应。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