Precision Prevention Research Program

精准预防研究计划

• 批准号: 10689700
• 负责人: Andrew T Chan
• 金额: $ 98.78万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10689700
• 关键词: Advanced Malignant Neoplasm; Adverse effects; Age; Aspirin; Award; Biological Markers; Cancer Patient; Cells; Chemoprevention; Clinic; Clinical; Clinical Trials; Data; Dedications; Dose; Effectiveness; Etiology; Future; Goals; Harm Reduction; Hemorrhage; Individual; Integration Host Factors; International; Intervention; Investigation; Malignant Neoplasms; Modeling; Molecular; Molecular Epidemiology; Oncology; Patients; Physicians; Population; Population Study; Prevention Research; Prevention approach; Prospective, cohort study; Recommendation; Reporting; Research; Research Personnel; Resolution; Risk Reduction; Source; System; Target Populations; Testing; United States Preventative Services Task Force; Validation; Work; anticancer activity; biobank; biomarker driven; cancer prevention; career; cohort; colorectal cancer prevention; colorectal cancer risk; cost efficient; empowerment; evidence base; gut microbiome; human data; human tissue; improved; individualized prevention; novel; novel strategies; personalized approach; prevent; preventive intervention; programs; rapid testing; research vision; risk stratification; risk/benefit ratio; tool

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

项目成果

Lifestyle and Environmental Approaches for the Primary Prevention of Hepatocellular Carcinoma.

• DOI: 10.1016/j.cld.2020.06.002
• 发表时间: 2020-11
• 期刊: Clinics in liver disease
• 影响因子: 5.1
• 作者: Simon TG;Chan AT
• 通讯作者: Chan AT

Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial.

• DOI: 10.1158/1940-6207.capr-21-0244
• 发表时间: 2022-06-02
• 期刊: Cancer prevention research (Philadelphia, Pa.)

Validity of continuous glucose monitoring for categorizing glycemic responses to diet: implications for use in personalized nutrition.

• DOI: 10.1093/ajcn/nqac026
• 发表时间: 2022-06-07
• 期刊: The American journal of clinical nutrition