Precision Prevention Research Program
精准预防研究计划
基本信息
- 批准号:10053438
- 负责人:
- 金额:$ 100.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:Advanced Malignant NeoplasmAdverse effectsAdvisory CommitteesAgeAspirinAwardBiological MarkersCancer PatientCellsChemopreventionClinicClinicalClinical TrialsDataDoseEffectivenessEtiologyFutureGoalsHarm ReductionHemorrhageIndividualIntegration Host FactorsInternationalInterventionInvestigationLeadMalignant NeoplasmsModelingMolecularMolecular EpidemiologyOncologyPatientsPhysiciansPopulationPopulation StudyPrevention ResearchPrevention approachPreventive InterventionPreventive serviceProspective cohort studyRecommendationReportingResearchResearch PersonnelResolutionRisk stratificationSourceSystemTarget PopulationsTestingValidationVisionWorkanticancer activitybasebiobankbiomarker-drivencancer preventioncareercohortcolorectal cancer preventioncolorectal cancer riskcost efficientevidence basegut microbiomehuman datahuman tissueimprovedindividualized preventionnovelnovel strategiespersonalized approachpreventprogramsrisk benefit ratiotool
项目摘要
PROJECT ABSTRACT
As an internationally recognized physician-investigator, I have dedicated my career to the prevention of
colorectal cancer (CRC). My most substantial contributions have influenced the evidence base supporting
aspirin’s effectiveness in reducing the risk of CRC and uncovered key molecular mechanisms underlying its anti-
cancer activity. This work has helped advance the field to a first-if-its-kind milestone recommendation for
population use of aspirin for cancer prevention by the US Preventive Services Task Force. However, growing
data demonstrates that the effect of aspirin may differ according to host factors, including the gut microbiome
and age, suggesting that a “one-size-fits-all” approach to aspirin chemoprevention is limited. Thus, developing
novel approaches to prevention through molecular risk stratification is a high priority. Building on my expertise
in molecular epidemiology, clinical trials, the gut microbiome, and clinical cancer prevention, my research vision
is to develop a comprehensive Precision Prevention Research Program (PPRP) through this NCI Outstanding
Investigator Award. The overarching goal of this PPRP is to leverage complementary sources of human data,
including population-based studies, clinical cohorts, and “living biobanks” to study the entire continuum from
healthy individuals to advanced cancer patients and with resolution from single cells to large populations to
acquire a more complete, multifaceted view of how interventions can be tailored to prevent cancer. Our PPRP
facilitates mechanistic discovery in population studies that can lead to rapid testing of novel, molecularly-inspired
biomarkers in clinical cohorts, creating opportunity for “living biobanks” for rigorous validation and advanced
mechanistic investigation. Moreover, this model is reciprocal. Our clinical cohorts and translational tools using
patient-derived experimental systems may also identify novel mechanisms that can be examined within the
context of our population studies to confirm their relevance to cancer and improve generalizability. Through this
R35, I will develop and expand this PPRP through expansion of my work in aspirin chemoprevention. Aspirin is
an exemplar agent to develop this platform since efficacy for CRC prevention has already been established and
its association with adverse effects, such as bleeding, necessitate a tailored approach. As the Lancet Oncology
Commission report concluded: “Perhaps the most promising precision-based approach to cancer prevention in
the near future involves molecular selection for repurposed low-dose aspirin” and “in view of aspirin’s potential
adverse effects (e.g., bleeding), tailoring aspirin use is a high priority”. By enhancing understanding of aspirin’s
mode of action, this proposal may lead to novel mechanistic biomarkers or complementary preventative
interventions that may maximize the benefits of aspirin while minimizing the harms. Over the long-term, I envision
that this work will provide proof-of-concept for expansion of the PPRP program as a cost-efficient platform within
which to move additional cancer preventive interventions rapidly into the clinic.
项目摘要
作为一名国际公认的医师研究员,我将我的职业生涯奉献给了预防
结直肠癌(CRC)。我最重要的贡献影响了支持的证据基础
阿司匹林在降低结直肠癌风险方面的有效性,并揭示了其抗结直肠癌的关键分子机制
癌症活动。这项工作帮助该领域取得了前所未有的里程碑建议:
美国预防服务工作组对阿司匹林用于预防癌症的人群使用情况进行了调查。然而,不断增长的
数据表明,阿司匹林的作用可能会因宿主因素(包括肠道微生物群)的不同而有所不同
和年龄,这表明“一刀切”的阿司匹林化学预防方法是有限的。因此,开发
通过分子风险分层进行预防的新方法是当务之急。以我的专业知识为基础
在分子流行病学、临床试验、肠道微生物组和临床癌症预防方面,我的研究愿景
旨在通过这项 NCI 杰出研究项目来制定全面的精准预防研究计划 (PPRP)
研究员奖。该 PPRP 的总体目标是利用人类数据的补充来源,
包括基于人群的研究、临床队列和“活体生物库”,以研究从
从健康个体到晚期癌症患者,以及从单细胞到大量细胞的分辨率
获得关于如何制定干预措施来预防癌症的更完整、多方面的观点。我们的计划
促进群体研究中的机制发现,从而快速测试新颖的、受分子启发的
临床队列中的生物标志物,为“活体生物库”创造了严格验证和先进的机会
机制调查。而且,这个模型是互惠的。我们的临床队列和转化工具使用
源自患者的实验系统还可以识别可以在内部进行检查的新机制
我们的人口研究背景,以确认其与癌症的相关性并提高普遍性。通过这个
R35,我将通过扩展我在阿司匹林化学预防方面的工作来开发和扩展这个 PPRP。阿司匹林是
由于 CRC 预防功效已经确立,因此开发该平台的典范代理
它与出血等不良反应相关,因此需要采取量身定制的方法。正如柳叶刀肿瘤学
委员会报告得出结论:“也许最有前途的基于精确的癌症预防方法
在不久的将来,涉及重新利用低剂量阿司匹林的分子选择”和“鉴于阿司匹林的潜力
不良反应(例如出血),调整阿司匹林的使用是重中之重”。通过加深对阿司匹林的了解
作用方式,该提案可能会产生新的机械生物标志物或补充性预防措施
可以最大限度地发挥阿司匹林益处同时最大限度地减少危害的干预措施。从长远来看,我设想
这项工作将为 PPRP 计划的扩展提供概念验证,作为一个具有成本效益的平台
从而将额外的癌症预防干预措施迅速推向临床。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Andrew T Chan其他文献
Turning up the heat on colorectal cancer
加大对结直肠癌的研究力度
- DOI:
10.1038/nm.2500 - 发表时间:
2011-10-11 - 期刊:
- 影响因子:50.000
- 作者:
Andrew T Chan - 通讯作者:
Andrew T Chan
ULTRA-PROCESSED FOOD CONSUMPTION AND RISK OF GALLSTONE DISEASE: ANALYSIS OF THREE PROSPECTIVE COHORTS.
超加工食品的消费和胆石病的风险:三个前瞻性队列的分析。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:7.1
- 作者:
Eugenia Uche;Jane Ha;Neha Khandpur;S. Rossato;Yiqing Wang;Long H Nguyen;Ming;E. Giovannucci;Andrew T Chan - 通讯作者:
Andrew T Chan
Andrew T Chan的其他文献
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{{ truncateString('Andrew T Chan', 18)}}的其他基金
Effects of inflammaging on intestinal epithelial cells and aspirin chemoprevention.
炎症对肠上皮细胞的影响和阿司匹林化学预防。
- 批准号:
10152090 - 财政年份:2021
- 资助金额:
$ 100.8万 - 项目类别:
Effects of inflammaging on intestinal epithelial cells and aspirin chemoprevention.
炎症对肠上皮细胞的影响和阿司匹林化学预防。
- 批准号:
10597250 - 财政年份:2021
- 资助金额:
$ 100.8万 - 项目类别:
Effects of inflammaging on intestinal epithelial cells and aspirin chemoprevention.
炎症对肠上皮细胞的影响和阿司匹林化学预防。
- 批准号:
10383683 - 财政年份:2021
- 资助金额:
$ 100.8万 - 项目类别:
Prebiotic effect of eicosapentaenoic acid treatment for colorectal cancer
二十碳五烯酸治疗结直肠癌的益生元作用
- 批准号:
10406256 - 财政年份:2020
- 资助金额:
$ 100.8万 - 项目类别:
Prebiotic effect of eicosapentaenoic acid treatment for colorectal cancer
二十碳五烯酸治疗结直肠癌的益生元作用
- 批准号:
10620849 - 财政年份:2020
- 资助金额:
$ 100.8万 - 项目类别:
Prebiotic effect of eicosapentaenoic acid treatment for colorectal cancer
二十碳五烯酸治疗结直肠癌的益生元作用
- 批准号:
10161752 - 财政年份:2020
- 资助金额:
$ 100.8万 - 项目类别:
ASPirin in Reducing Events in the Elderly - eXTension
阿司匹林在减少老年人事件中的作用 - eXTension
- 批准号:
10428600 - 财政年份:2019
- 资助金额:
$ 100.8万 - 项目类别:
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