Exosomal RNA: A Novel Signature Guide for Prostate Cancer Proton Therapy

外泌体 RNA：前列腺癌质子治疗的新特征指南

• 批准号: 10492759
• 负责人: Simone Olivia Heyliger
• 金额: $ 7.86万
• 依托单位: HAMPTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10492759
• 关键词: Achievement; African American population; Area; Biological Markers; Biopsy; Blood; Blood specimen; Body Fluids; Cancer Patient; Cells; Cerebrospinal Fluid; Cessation of life; Clinical; Collaborations; DNA; Data; Decision Making; Detection; Development; Disease; European; Evaluation; Excision; Feasibility Studies; Future; Genes; Genetic; Genomics; Goals; Grant; Health; Historically Black Colleges and Universities; Human; Institutes; Joints; Legal patent; Lipids; Liquid substance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Measures; Messenger RNA; Modality; Molecular; Monitor; Neoplasm Metastasis; Newly Diagnosed; Normal Cell; Operative Surgical Procedures; Outcome; Outcomes Research; Patients; Physicians; Preparation; Process; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic; RNA; Radiation Monitoring; Radiation therapy; Radical Prostatectomy; Recurrence; Research; Research Infrastructure; Rest; Risk; Risk Assessment; Saliva; Sampling; Site; Testing; Time Study; Tissues; Toxic effect; Universities; Urine; Urologic Oncology; Urology; Vesicle; Virginia; Work; anticancer research; base; cancer genomics; clinical decision-making; cohort; detection method; exosome; extracellular vesicles; follow-up; improved; liquid biopsy; medical schools; men; microvesicles; neoplastic cell; non-invasive monitor; novel; particle; prognostic; prostate biopsy; protein metabolite; proton therapy; recruit; response; response biomarker; serum PSA; specific biomarkers; tool; trafficking; treatment response; tumor; tumor microenvironment; unnecessary treatment

Project Summary / Abstract Proton therapy (PT) is a form of radiation therapy used to treat prostate cancer patients that can be an alternative to surgery. While PT is thought to risk less toxicity than conventional radiation therapy, much about PT is still not understood. To help serve their local area of tidewater Virginia, which has one of the highest rates of prostate cancer in the world, especially in African-Americans, Hampton University (HU), a Historically Black University, has opened the Hampton University Proton Therapy Institute. To help build the research capacity at HU, leveraging their clinical expertise in proton therapy, the Icahn School of Medicine at Mount Sinai (ISMMS) and HU propose this joint project aimed at developing a noninvasive biomarker for response to PT. The team at ISMMS will bring their expertise in genomics and exosome profiling, a noninvasive way to measure particles that are thought to shed from the tumor, to this project and in the process help build the research capacity at HU. The research goal of this project is to determine changes in the exosomal RNA (exoRNA) profile of exosomes taken from prostate cancer patients before and after radiotherapy with PT. All aims of the study use patient samples collected at the HUPTI by the HU team. In aim 1, we will ask if an exosomal signature of radical prostatectomy shows similar changes before and after PT. In aim 2, to determine if there are specific changes in the mRNA profile in response to PT, we will globally profile RNA isolated from exosomes before and after PT. In aim 3, to continue to build this project in preparation for a future collaborative R01 submission, we will recruit additional patients from HUPTI to this study and obtain blood specimens before, during, and after PT. At the end of the study time period, our scientific achievement will have been to determine what changes in the RNA profile of exosomes can be observed in response to PT. This will be important preliminary data demonstrating the utility of exosomes for noninvasive monitoring of PT. More importantly, through this collaborative partnership between ISMMS and HU, we will have enhanced the research infrastructure of HU in a way that will allow HU to pursue further research both jointly with ISMMS and independently building on their clinical expertise in proton therapy.

项目总结/摘要 质子疗法（PT）是用于治疗前列腺癌患者的放射疗法的一种形式，其可以是治疗前列腺癌的有效方法。 替代手术。虽然PT被认为比传统的放射治疗具有更低的毒性，但许多关于 PT仍然不被理解。帮助他们服务于当地的弗吉尼亚州，那里有最高的 汉普顿大学（HU）的一项研究显示，世界上前列腺癌的发病率，特别是非洲裔美国人的发病率， 布莱克大学开设了汉普顿大学质子治疗研究所。帮助建立研究 在胡的能力，利用他们在质子治疗的临床专业知识，伊坎医学院在山 Sinai（ISMMS）和HU提出了这个联合项目，旨在开发一种非侵入性生物标志物， PT. ISMMS的团队将带来他们在基因组学和外泌体分析方面的专业知识，这是一种非侵入性的方法， 测量被认为是从肿瘤脱落的颗粒，这个项目，并在这个过程中帮助建立 研究能力在胡。该项目的研究目标是确定外泌体RNA的变化， 图10示出了在用PT进行放射治疗之前和之后从前列腺癌患者获取的外泌体的外泌体RNA（exoRNA）谱。所有 这项研究的目的是使用HU团队在HUPTI收集的患者样本。在目标1中，我们会问， 外泌体标记在根治性直肠癌切除术前后显示相似的变化。在目标2中， 确定是否有特定的变化，在mRNA谱响应PT，我们将在全球范围内分析RNA 在PT之前和之后从外泌体分离。在目标3中，继续建设该项目，为 未来的合作R 01提交，我们将从HUPTI招募更多患者参与本研究，并获得 PT之前、期间和之后的血液标本。在研究结束时，我们的科学成就 将是确定外泌体的RNA谱中的哪些变化可以在对PT的响应中观察到。 这将是证明外泌体用于PT的非侵入性监测的重要初步数据。 更重要的是，通过ISMMS和HU之间的合作伙伴关系，我们将加强 胡的研究基础设施的方式，这将使胡追求进一步的研究都与ISMMS联合， 他们在质子治疗方面的临床专业知识。