Early Phase Clinical Cancer Prevention Consortium

早期临床癌症预防联盟

• 批准号: 10683160
• 负责人: Dean E. Brenner
• 金额: $ 153.89万
• 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/10683160
• 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; Collaborations; Colon; Colon Carcinoma; Conduct Clinical Trials; Data; Dose; Ensure; Environment; Epidemic; Epigenetic Process; 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; Institution; Interruption; Iron Chelation; 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; Organizational Affiliation; Oxidative Stress; Participant; Pathway interactions; Patient Recruitments; Pharmaceutical Preparations; Phase; Play; Prevention; Prevention strategy; Prevention trial; Preventive; Process; Proliferating; Prostate; Protocols documentation; Regulation; Resources; Role; STAT3 gene; Safety; Sampling; Schedule; Science; Site; Solid Neoplasm; Source; Speed; Stress; System; Technology; Testing; Therapeutic; Therapeutic Index; Tissue Sample; Tissues; Universities; Vision; biomarker driven; breast density; cancer cell; cancer prevention; cancer risk; cancer stem cell; carcinogenesis; cell type; cellular targeting; cytokine; design; drug repurposing; drug testing; dysbiosis; early phase clinical trial; early phase trial; experience; 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 cell self renewal; stem cells; stem-like cell; stemness; synergism; targeted agent; trial design; tumor initiation

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.

项目摘要 早期临床癌症预防联盟建议制定，实施，并完成早期 针对干细胞的临床试验大多数癌症显示出一种层次结构， 干细胞群是“干细胞样的”。炎症应激驱动干细胞自我更新增加 不同的器官部位慢性炎症应激的来源包括肥胖、爆炸（酒精、化学品）， 感染因子、微生物生态失调和遗传多态性。其中，肥胖相关的代谢 相关的综合症正达到流行病的程度。这个联盟提出了一个总体假设 炎症诱导的组织基质环境的变化增加了干细胞的自我更新， 上皮间质转化这些变化可以通过生物标志物驱动的给药逆转或抑制 临床预防剂，单独或组合。我们选择针对不良代谢的药物， 炎症暴露导致的环境和驱动干细胞增殖。联合会建议， 以下目标：1.每年至少制定并提交三份关于早期试验的提案， 预防肥胖相关的癌症（结肠癌、下食道癌、乳腺癌、前列腺癌、膀胱癌）; 2.进行1至3 在赠款的财政能力范围内，每年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 获得机械原理证明数据;以及3.管理研究操作的所有方面，同时遵守 遵守临床试验实施的所有适用规则和法规。密歇根大学Rogel Cancer 中心是一个由9个机构组成的联盟的牵头组织，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使我们能够 深度的智力参与与参与者招募和保留的经验丰富的后勤相结合， 以及NCI支持的癌症中心提供的基础设施支持。我们已经建立了程序， 确保意向书和方案文件的快速周转，统一的样品处理、管理和 运输和快速分析生物样品。该联盟将与CP-CTNet的其他联盟合作 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用于 在癌症风险增加的个体中进行的III期试验。

项目成果

How Does Obesity Drive Human Carcinogenesis? Challenges in Dissecting the Mechanisms of Adipose-Epithelial Signaling.

肥胖如何导致人类致癌？

• DOI: 10.1158/1940-6207.capr-20-0367
• 发表时间: 2020
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Colacino,Justin;Djuric,Zora;Brenner,DeanE
• 通讯作者: Brenner,DeanE