Early Phase Clinical Cancer Prevention Consortium

早期临床癌症预防联盟

• 批准号: 10002730
• 负责人: Dean E. Brenner
• 金额: $ 96.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-07 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10002730
• 关键词: Address; Alcohols; Antibodies; Automobile Driving; Back; Biological Markers; Biology; Bladder; Breast; CDC2 gene; Cancer Center; Cancer Prevention Trial; Chemicals; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Colon; Colon Carcinoma; Conduct Clinical Trials; Data; Dose; Ensure; Environment; Epidemic; Epigenetic Process; Epithelial; Epithelial Cells; Epithelium; Esophageal Tissue; Esophagus; Funding; Genes; Genetic; Genetic Polymorphism; Genitourinary system; Goals; Grant; In Situ; Individual; Infectious Agent; Inflammation; Inflammation Mediators; Inflammatory; Infrastructure; Institutes; Institution; Interruption; Investigation; Iron Chelating Agents; JAK1 gene; Lead; Letters; Life Style; Link; Logistics; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Measures; Mesenchymal; Metabolic; Metabolic syndrome; Methodology; Methods; Michigan; Molecular; Molecular Target; Neoplasms; New Agents; Normal Cell; Obesity; Obesity associated cancer; Organ; Oxidative Stress; Participant; Pathway interactions; Patient Recruitments; Pharmaceutical Preparations; Phase; Play; Prevention; Prevention strategy; Prevention trial; Preventive; Process; Prostate; Protocols documentation; Regulation; Resources; Role; STAT3 gene; Safety; Sampling; Schedule; Science; Ships; Site; Solid Neoplasm; Source; Speed; Stress; System; Technology; Testing; Therapeutic; Therapeutic Index; Tissue Sample; Tissues; Universities; Vision; base; biomarker-driven; breast density; cancer cell; cancer prevention; cancer risk; cancer stem cell; carcinogenesis; cell type; cellular targeting; cytokine; design; drug testing; dysbiosis; early phase clinical trial; early phase trial; experience; high risk; high risk population; high throughput technology; human tissue; immune activation; malignant breast neoplasm; microbial; mortality; neoplastic; novel; novel strategies; obesity prevention; operation; participant retention; pharmacokinetics and pharmacodynamics; phase III trial; preclinical study; prevent; progenitor; programs; promoter; receptor; response; self-renewal; sound; stem cell population; stem cell proliferation; stem cells; stem-like cell; stemness; synergism; targeted agent; trial design; tumor

Project Summary The Early Phase Clinical Cancer Prevention Consortium proposes to develop, implement, and complete early clinical trials targeting cellular stemness. Most cancers display a hierarchical organization that is driven by a population of cells that are “stem-like”. Inflammatory stress drives increased stem cell self-renewal across different organ sites. The sources of chronic inflammatory stess include obesity, explosures (alcohol, chemicals), infectious agents, microbial dysbiosis, and genetic polymorphisms. Of these, the obesity-associated metabolic syndrome associated is reaching epidemic proportions. This consortium addresses the overarching hypothesis that inflammatory-induced shifts in the tissue stromal environment increase stem cell self-renewal and enhance epithelial mesenchymal transformation. These shifts can be reversed or dampened by biomarker driven dosing of clinical preventive agents, either alone or in combination. We select agents that target the adverse metabolic milieu resulting from inflammatory exposures and driving stem cell proliferation. The Consortium proposes the following aims: 1. To develop and submit at least three proposals each year for early phase trials for the prevention of obesity-related cancers (colon, lower esophagus, breast, prostate, bladder); 2. To conduct 1 to 3 early phase cancer prevention trials per year within the fiscal capacity of the grant that include evaluating translational endpoints in biospecimens, asssessing the pharmacokinetics and pharmacodynamics, and obtaining mechanistic proof-of-principle data; and 3. To manage all aspects of study operations while complying with all applicable rules and regulations for the conduct of clinical trials. The University of Michigan Rogel Cancer Center is the lead organization of a consortium consisting of 9 institutions of which all are within NCI Core Funded Cancer Centers. The intellectual diversity and strong academic accomplishement of our consortium permits deep intellectual engagement combined with the experienced logistics of participant recruitment and retention, and the infrastructure support available in NCI supported cancer centers. We have established processes to ensure rapid turn-around of letters of intent and protocol documents, uniform sample handling, management and shipment, and rapid analysis of biosamples. The Consortium will collaborate with other the CP-CTNet consortia to create synergies of science and resources, enabling paradigm shifts that rapidly test and prioritize agents for Phase III trials conducted in individuals at increased risk of cancer.

项目概要 早期临床癌症预防联盟提议尽早制定、实施和完成 大多数针对细胞干性的临床试验显示出由细胞驱动的分层组织。 “类似干细胞”的细胞群会促进干细胞的自我更新。 不同器官部位的慢性炎症应激的来源包括肥胖、接触（酒精、化学品）、 传染源、微生物失调和遗传多态性，其中，与肥胖相关的代谢。 相关综合症已达到流行病的程度，该联盟提出了这一总体假设。 炎症诱导的组织基质环境变化增加干细胞的自我更新并增强 这些转变可以通过生物标志物驱动的剂量来逆转或抑制。 我们选择针对不良代谢的药物，无论是单独使用还是联合使用。 该联盟提出了由炎症暴露和驱动干细胞增殖引起的环境。 目标如下： 1. 每年制定并提交至少三项早期试验提案 预防与肥胖相关的癌症（结肠癌、下食道癌、乳腺癌、前列腺癌、膀胱癌）；进行1至3项； 每年在拨款的财政能力范围内进行早期癌症预防试验，包括评估 生物样本中的转化终点，评估药代动力学和药效学，以及 获取机械原理验证数据；以及 3. 在遵守规定的同时管理研究操作的各个方面； 遵守进行临床试验的所有适用规则和规定。 中心是由 9 个机构组成的联盟的牵头组织，其中所有机构均属于 NCI 核心资助范围 我们联盟的知识多样性和强大的学术成就允许癌症中心。 深度的智力参与与参与者招募和保留方面经验丰富的后勤工作相结合， 以及 NCI 支持的癌症中心提供的基础设施支持，我们已经建立了流程。 确保意向书和协议文件的快速周转，统一的样品处理、管理和 该联盟将与其他 CP-CTNet 联盟合作。 创造科学和资源的协同作用，实现范式转变，快速测试和优先考虑代理 在癌症风险增加的个体中进行的 III 期试验。