Radiation Oncology-Biology Integration Network on Oligometastasis (ROBIN OligoMET) Center

转移是一个复杂的系统问题，具有跨越细胞、组织、器官和生物体的关键变化。 目前治疗转移性肿瘤的疗效有限，这说明我们对转移性肿瘤的认识还不够深入。 前列腺癌(PCA)的转移能力表现为一系列疾病，其中包含 转移在数量和位置上受限的少转移状态。所有肿瘤的放射巩固 用于预防进一步进展的少转移性前列腺癌的沉积现在得到了一项小型随机研究的支持 循环设置，但在从头开始空间中的效用未知。这些是重要的早期临床数据。 提示低转移状态的存在和辐射巩固在改变中的重要性 潜在的转移倾向，对这些患者的治疗有直接影响。我们的U54 罗宾寡转移中心汇聚了来自密歇根大学的杰出教员。 马里兰大学(UM)、威尔·康奈尔医学院(WCM)和托马斯·杰斐逊大学(TJU)共同研究 放射治疗(RT)如何影响新发的少转移前列腺癌的转移过程。这 多学科视角使我们能够将最新的临床试验、概况分析和计算方法带到 与少转移的临床最相关的方面有关。这反过来将导致新的 使用RT对抗转移的方法。这个U54罗宾寡头中心将由Phuoc博士领导 Tran，Nicole Simone和Amit Sawant(MPI)。项目领导层由在以下领域具有丰富背景的教职员工组成 辐射生物学、物理学和转移研究：项目1(基因组学、放射组学和液体活检) 作者：Tran，Ren和Sawant博士；项目2(代谢组学和差异)由Simone博士领导；资源 分享和交叉培训核心由路易吉·马尔基奥尼博士、萨旺特博士和任博士领导。我们带来了各种各样的 模型系统、实验方法和概念框架。这些项目融合了最先进的技术 来自人类的组织、液体和放射学多参数图谱技术与同基因 第一人2期随机试验背景下的小鼠肿瘤模型。数据将使用新颖的 网络方法，以确定跨项目功能验证的候选对象的优先顺序。科学和后勤 整合将由一个管理核心来确保。多组学分析与整合，定量成像 分析，网络分析将在交叉培训核心进行。罗宾寡妇中心将 验证巩固辐射可以改变癌细胞状态、可塑性和宿主-肿瘤的全球假设 驱动转移形成的新陈代谢。目标1-确定癌细胞本身和肿瘤微环境 改变转移倾向的辐射调节的可塑性机制。目标2-确定新陈代谢 非裔美国人与高加索人少转移瘤患者中调节抗肿瘤免疫和转移的变化 SABR巩固后的前列腺癌。目标#3-嵌入培训举措的多尺度整合 旨在阐明巩固SABR后转移性癌症的新的治疗脆弱性。

Metastasis is a complex systems problem, with critical changes across cell, tissue, organ, and organism scales. The limited efficacy of current therapies in metastatic patients argues that we do not fully understand metastasis. The metastatic capacity of prostate cancer (PCa) behaves along a spectrum of disease that contains an oligometastatic state where metastases are limited in number and location. Radiation consolidation of all tumor deposits in oligometastatic PCa to forestall further progression is now backed by small randomized studies in the recurrent setting, but the utility in the de novo space is unknown. These are important early clinical data suggesting the existence of an oligometastatic state and the importance of radiation consolidation in altering underlying metastatic proclivity which has immediate impact for the management of these patients. Our U54 ROBIN Oligometastasis (ROBIN OligoMET) Center brings together pre-eminent faculty from the University of Maryland (UM), Weill Cornell Medicine (WCM) and Thomas Jefferson University (TJU) to study mechanisms of how radiation therapy (RT) can affect the metastatic process in de novo oligometastatic PCa. This multidisciplinary perspective enables us to bring the latest clinical trial, profiling and computational methods to bear on the most clinically relevant aspects of oligometastasis. This in turn will lead to the development of new approaches for using RT to combat metastases. This U54 ROBIN OligoMET Center will be led by Drs. Phuoc Tran, Nicole Simone and Amit Sawant (MPI). Project leadership comprises faculty with strong backgrounds in radiation biology, physics and metastasis research: Project 1 (Genomics, radiomics and liquid biopsies) is led by Drs. Tran, Ren and Sawant; Project 2 (Metabolomics and disparities) is led by Dr. Simone; and the Resource Sharing and Cross-Training Cores are led by Drs. Luigi Marchionni, Sawant and Ren. We bring a diversity of model systems, experimental methods, and conceptual frameworks. The projects integrate state-of-the-art tissue, liquid and radiomic multi-parametric profiling techniques from humans complimented with syngeneic mouse tumor models in the context of a first-in-man phase 2 randomized trial. Data will be integrated using novel network methods to prioritize candidates for functional validation across projects. Scientific and logistical integration will be ensured by an Administrative Core. Multi-omics analysis and integration, quantitative image analysis, and network analysis will be conducted in the Cross-Training Core. The ROBIN OligoMET Center will test the global hypothesis that consolidative radiation can alter cancer cell state plasticity and host-tumor metabolism that drives metastasis formation. AIM #1 – Identify cancer cell intrinsic and tumor microenvironment plasticity mechanisms modulated by radiation that change metastatic proclivity. AIM #2 – Determine metabolic changes that regulate anti-tumor immunity and metastasis in African American versus Caucasian oligometastatic prostate cancer following SABR consolidation. AIM #3 – Multi-scale integration embedded with training initiatives towards the elucidation of novel therapeutic vulnerabilities of metastatic cancers following consolidative SABR.