Early Phase Clinical Cancer Prevention Consortium

项目摘要 早期临床癌症预防联盟建议及早开发、实施和完成 针对细胞干细胞的临床试验。大多数癌症表现出一种等级组织，这种组织由一种 成群的“干细胞样”细胞。炎性应激促进整个干细胞的自我更新 不同的器官部位。慢性炎症应激的来源包括肥胖、暴露(酒精、化学物质)、 感染源、微生物失调和遗传多态。其中，与肥胖相关的代谢 相关的综合症正在达到流行的程度。这个联盟解决了最重要的假设 炎症诱导的组织基质环境的改变增加了干细胞的自我更新和增强 上皮间充质转化。这些变化可以通过生物标志物驱动的剂量来逆转或抑制 临床预防药物，无论是单独使用还是联合使用。我们选择针对不良新陈代谢的药物 炎性暴露和推动干细胞增殖所造成的环境。该财团建议 以下目标：1.每年至少制定和提交三项提案，以进行早期试验 预防肥胖相关癌症(结肠癌、下段食道癌、乳腺癌、前列腺癌、膀胱癌)；2.开展1至3项工作 在赠款的财政能力范围内每年进行的早期癌症预防试验，包括评估 生物类群中的翻译终点，药代动力学和药效学的评估，以及 获得机械性的原则证明数据；以及3.在遵守的同时管理研究操作的所有方面 以及所有适用于进行临床试验的规则和条例。密歇根大学罗杰尔癌症 中心是一个由9个机构组成的财团的牵头组织，所有这些机构都在NCI核心资助范围内 癌症中心。我们联盟的知识多样性和强大的学术成就允许 深度的智力投入与参与者招募和留住的经验丰富的后勤相结合， NCI提供的基础设施支持支持癌症中心。我们已经建立了流程，以 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 运输，以及生物样本的快速分析。该财团将与CP-CTNet财团进行合作 创造科学和资源的协同效应，实现范式转变，快速测试和确定代理的优先顺序 第三阶段试验是在癌症风险增加的个体中进行的。

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.