United for Health Equity - Living PDX Program (U4HELPP)

United for Health Equity - Living PDX 计划 (U4HELPP)

基本信息

批准号：
10733310
负责人：
Joshua (Chuck) Harrell
金额：
$ 103.1万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-19 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10733310
关键词：
Address Advanced Malignant Neoplasm Affect Award Bioinformatics Biometry Black Populations Black race Breast Breast Cancer Detection Cancer Biology Cancer Center Cancer Etiology Cancer Model Cellular biology Cessation of life Clinic Clinical Clinical Investigator Clinical Management Clinical Research Clinical Trials Colon Communication Communities Cryopreservation Data Development Diagnosis Discipline Disease Disparity Environment Epidemiology Ethnic Population Fostering Foundations Funding Generations Genes Genetic Genomics Goals Grant Growth Gynecologic Health Health Disparities Research Incidence Institution Investigational Drugs Liver Lung Malignant Female Reproductive System Neoplasm Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Malignant neoplasm of pancreas Mediating Metadata Minority Groups Modeling Molecular Molecular Profiling Neoplasm Metastasis Oncology Pancreas Pancreatic Adenocarcinoma Pathway interactions Patients Peritoneal Peritoneal Diseases Pharmaceutical Preparations Pharmacology Pharmacotherapy Pilot Projects Population Heterogeneity Positioning Attribute Pre-Clinical Model Proteins Proteomics Race Refractory Research Research Personnel Research Project Grants Research Support Resources Role Structure Surgeon System Testing Therapeutic Translating Translational Research Underrepresented Minority Underrepresented Populations biomedical referral center black patient black women cancer health disparity cancer type cohort disorder subtype epigenetic regulation ethnic disparity ethnic diversity experience gastrointestinal health disparity health equity improved innovation insight inter-institutional malignant breast neoplasm molecular subtypes mortality multidisciplinary novel novel drug combination novel therapeutic intervention patient derived xenograft model patient population peritoneal cancer pre-clinical precision medicine programs prospective proteogenomics racial disparity racial diversity racial health disparity racial population repository research study response safety net targeted treatment therapeutic evaluation therapeutically effective treatment response triple-negative invasive breast carcinoma tumor understudied cancer

项目摘要

PROJECT SUMMARY/ABSTRACT – OVERALL The United for Health Equity-Living PDX Program (U4HELPP) seeks to develop >500 new patient-derived xenograft (PDX) models of cancers originated from the breast, pancreas, colon, liver, lung, and other advanced peritoneal cancers. These PDXs will be made from >60% of patients from underrepresented populations which our safety-net clinical system serves. To develop such a large number and diverse set of PDXs, we have enlisted the support of a set of surgeons that specialize in each cancer type. Once extracted, the tumors are immediately provided to the U4HELPP PDX Core which functions to propagate, distribute, and cryopreserve them. Successfully generated PDXs will be subjected to genomic characterization and quantitative ancestral profiling by the U4HELPP Bioinformatics Core so that we can better understand how ancestry contributes to genetics and responses to targeted therapeutics. The PDXs will be provided to two Research Projects, that will focus on either pancreatic cancer or breast cancer. The Pancreatic Cancer project will generate large-scale proteomics insights from over 200 PDXs to refine subtypes of the disease and identify more effective therapeutics from Black and White patients. The Breast Cancer project will utilize 20 PDXs that are Basal-like breast cancers, characterize their metastatic profiles, define proteogenomic pathways that mediate metastatic growth, and target metastases with synergistic investigational new drug combinations. The information from these PDXs and Projects will be shared with the U4HELPP Pilot Projects and Trans-Network Activities Core which will award Pilot Project grants to utilize the PDXs generated by us and our partnering PDXNet institutions. All of the PDXs and insights gained will be shared with the NCI with the goal of reducing cancer disparities. Through this team effort we are confident that we will be able to develop these unique resources and generate significant preliminary data that will support investigator initiated clinical trials at the Massey Cancer Center.

项目概要/摘要——总体 United for Health Equity-Living PDX 计划 (U4HELPP) 寻求开发超过 500 种新的源自患者的源自乳腺癌、胰腺癌、结肠癌、肝癌、肺癌和其他晚期癌症的异种移植（PDX）模型这些腹膜癌将由超过 60% 的患者组成，这些患者来自代表性不足的人群。我们的安全网临床系统服务于开发如此大量且多样化的 PDX。在一组专门治疗每种癌症类型的外科医生的支持下，肿瘤一旦被切除，就会立即被切除。提供给 U4HELPP PDX 核心，其功能是传播、分发和冷冻保存它们。成功生成的 PDX 将进行基因组表征和定量祖先分析由 U4HELPP 生物信息学核心提供，以便我们能够更好地了解血统如何对遗传学做出贡献 PDX 将提供给两个研究项目，该项目将重点关注胰腺癌或乳腺癌项目将产生大规模的蛋白质组学。来自 200 多个 PDX 的见解，以细化疾病的亚型并从 Black 中找出更有效的治疗方法乳腺癌项目将利用 20 种类似基底乳腺癌的 PDX，描述其转移特征，定义介导转移生长的蛋白质基因组通路，并靶向来自这些 PDX 的信息和协同研究新药组合的转移。项目将与 U4HELPP 试点项目和跨网络活动核心共享，后者将授予试点项目项目拨款用于利用我们和我们的合作 PDXNet 机构生成的 PDX。所获得的见解将与 NCI 分享，旨在通过该团队的努力减少癌症差异。我们相信，我们将能够开发这些独特的资源并产生重要的初步成果数据将支持研究者在梅西癌症中心发起的临床试验。