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

寡转移放射肿瘤学-生物学整合网络 (ROBIN OligoMET) 中心

基本信息

批准号：
10676851
负责人：
Amit Sawant
金额：
$ 147.49万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-04 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10676851
关键词：
Affect African American Baltimore Biological Models Biology Caucasians Cells Clinical Data Clinical Trials Complex Computing Methodologies DNA Data Data Analyses Deposition Development Disease Disparity Disseminated Malignant Neoplasm Distant Ensure Evaluation Faculty Failure Funding Genomics Grant Human Image Analysis Immune Immune Evasion Immune response Institution Intervention Invaded Joints Leadership Liquid substance Location Malignant neoplasm of prostate Maryland Medicine Metabolic Metabolism Methods Microscopic Modeling Molecular Mus Neoplasm Circulating Cells Neoplasm Metastasis Organ Organism Pathway Analysis Patients Pattern Phase Physics Plasma Progression-Free Survivals Proteomics RNA Radiation Radiation Oncology Radiation therapy Radiobiology Randomized Recording of previous events Recurrence Research Research Project Grants Resource Sharing Sampling System Techniques Testing Time Tissues Training Tumor Immunity Universities Validation cancer cell candidate identification clinically relevant combat design experience first-in-human in vivo innovation liquid biopsy metabolomics metastatic process mouse model multidisciplinary multiple omics new therapeutic target novel novel strategies novel therapeutics quantitative imaging radiomics randomized trial tumor tumor behavior tumor metabolism tumor microenvironment

项目摘要

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.

转移是一个复杂的系统问题，在细胞、组织、器官和生物体尺度上发生重大变化。目前的疗法对转移性患者的疗效有限，这表明我们尚未完全了解转移。前列腺癌 (PCa) 的转移能力表现为一系列疾病，其中包含寡转移状态，其中所有肿瘤的转移数量和位置均有限。现在通过小规模支持的随机研究，在寡转移性 PCa 中沉积以阻止进一步进展。复发的情况，但在从头领域的效用尚不清楚，这些都是重要的早期临床数据。表明寡转移状态的存在以及放射巩固在改变肿瘤转移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。 ROBIN Oligometasis (ROBIN OligoMET) 中心汇集了来自英国大学的杰出教师马里兰州 (UM)、威尔康奈尔医学院 (WCM) 和托马斯·杰斐逊大学 (TJU) 合作研究机制放射治疗 (RT) 如何影响新发寡转移性 PCa 的转移过程。多学科视角使我们能够将最新的临床试验、分析和计算方法引入与寡转移的临床最相关的方面有关，这反过来将导致新的发展。该 U54 ROBIN OligoMET 中心将由 Phuoc 博士领导。 Tran、Nicole Simone 和 Amit Sawant (MPI) 的教师均具有深厚的背景。放射生物学、物理学和转移研究：领导项目1（基因组学、放射组学和液体活检）由 Tran、Ren 和 Sawant 博士负责；项目 2（代谢组学和差异）由 Simone 博士和 Resource 领导；共享和交叉培训核心由 Luigi Marchionni、Sawant 和 Ren 博士领导。这些项目整合了最先进的模型系统、实验方法和概念框架。来自人类的组织、液体和放射多参数分析技术得到了同基因的称赞首次人体二期随机试验中的小鼠肿瘤模型数据将使用新颖的方法进行整合。网络方法来优先考虑跨项目功能验证的候选者。多组学分析和整合、定量图像将确保整合。 ROBIN OligoMET 中心将在交叉培训核心中进行分析和网络分析。检验巩固放射可以改变癌细胞状态可塑性和宿主肿瘤的整体假设驱动转移形成的新陈代谢 AIM #1 – 识别癌细胞内在和肿瘤微环境。由辐射调节的可塑性机制改变了转移倾向 AIM #2 – 确定代谢。非洲裔美国人与白种人寡转移中调节抗肿瘤免疫和转移的变化 SABR 巩固后的前列腺癌 AIM #3 – 嵌入培训计划的多尺度整合。阐明巩固性 SABR 后转移性癌症的新治疗弱点。