GI Cancer Genetics Research Program

胃肠道癌症遗传学研究计划

基本信息

批准号：
10380713
负责人：
SANFORD D. MARKOWITZ
金额：
$ 5.51万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-08-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10380713
关键词：
Address Adoption African American population Aspirin Award Barrett Esophagus Big Data Biological Markers Biometry Cancer Center Cancer Center Support Grant Cancer Detection Cancer Patient Chromatin Clinical Clinical Research Clinical Trials Collaborations Colon Carcinoma Colonic Neoplasms Colorectal Cancer Comprehensive Cancer Center DNA DNA Methylation Detection Development Diagnosis Direct Costs Drug usage Early Detection Research Network Early Diagnosis Epidemiology Epigenetic Process Esophageal Adenocarcinoma Esophageal Neoplasms Esophagus Ethnic Origin Faculty Feces Follow-Up Studies Foundations Funding Gene Mutation Genetic Genetic Research Genomics Germ-Line Mutation Goals Grant Health Professional Individual Leadership Malignant Neoplasms Malignant neoplasm of esophagus Malignant neoplasm of gastrointestinal tract Malignant neoplasm of pancreas Methods Modeling Mutation National Cancer Advisory Board Nurses&apos Health Study Organoids Pathway interactions Peer Review Phase II Clinical Trials Predisposition Prevention Prognosis Program Research Project Grants Proteomics Protocols documentation Publications Publishing Race Recommendation Research Personnel Research Project Grants Resistance Resource Sharing Role Science Systems Biology Technology Translating Tumor Suppressor Proteins Validation Work anticancer research base bioinformatics tool biomarker-driven cancer cell cancer chemoprevention cancer genetics cancer therapy carcinogenesis causal variant clinical development clinical implementation cohort colorectal cancer screening drug response prediction early detection biomarkers early phase clinical trial epigenetic marker epigenome gene environment interaction genome editing in vivo Model innovation interest malignant phenotype member mutant new therapeutic target novel novel strategies novel therapeutic intervention novel therapeutics pre-clinical research predictive marker programs racial disparity recruit screening small molecule inhibitor stem cells success therapeutic development therapeutic target tissue resource working group

项目摘要

GASTROINTESTINAL CANCER GENETICS RESEARCH PROGRAM PROJECT SUMMARY/ABSTRACT The Gastrointestinal Cancer Genetics (GICG) Research Program is a basic discovery program with a strong translational focus. The overarching goals of the GICG program are to discover genetic and epigenetic causes of GI cancers and to translate these discoveries into development of novel therapeutic approaches and biomarkers for early detection, prevention, diagnosis, prognosis and prediction of drug responses for GI cancers. The program is organized around 3 scientific aims: (1) Discover and clinically translate genetic alterations in GI cancers; (2) Discover and clinically translate epigenetic changes in GI cancers; and (3) Develop novel methods and models to facilitate basic and translational GI cancer research. The aims reflect the programs work to continue to: i) make groundbreaking discoveries in the genetic and epigenetic causes of GI cancers, and ii) achieve major clinical impact by translating these discoveries into new approaches for cancer detection, prevention, and treatment resulting in working groups and initiatives that coalesces program members with other cancer center investigators through interprogrammatic collaborations that result in preclinical and clinical research efforts, grants, and trial protocols. Extensive use of an array of shared resources, in particular, Genomics, Biostatistics, and Tissue Resources facilitate all aspects of member discoveries. Under the leadership of Sanford Markowitz (Co-Leader) and Zhenghe (John) Wang (Co-Leader) the GICG Program includes 18 full members and 3 associate members. Members represent 11 departments, and 83% of members are funded by 64 projects that give rise to a total of $5.5M in research grant funding (annual direct costs), of which $5.1M is peer-reviewed and $3.8M is NCI-funded. Between 2012 and 2016, GICG program members published 534 publications. Cancer and program related publications included 28% inter- programmatic, 18% intra-programmatic, 8% inter- and intra-programmatic and 8% that involved collaboration with another Cancer Center. This highly effective program has made major practice-changing contributions benefiting cancer patients. Examples include: i) an ongoing investigator-initiated (and Stand Up To Cancer [SU2C] supported) clinical trial of a novel targeted therapy for PI3KCA mutant CRCs; ii) an ongoing investigator-initiated clinical trial for biomarker driven detection of Barret’s esophagus; iii) FDA approval and commercial adoption of stool DNA screening for CRC based on detecting methylated DNA, an approach pioneered by GICG investigators and continued in an ongoing investigator-initiated clinical trial; iv) validation in two iconic epidemiology cohorts – the Nurses’ Health Study and the Health Professionals Follow-Up Study – of the discovery of a predictive biomarker of sensitivity or resistance to colon cancer chemoprevention by aspirin; and v) adoption by the NCI NEXT program of clinical development of a small molecule inhibitor of 15-PGDH invented by GICG investigators.

胃肠道癌遗传学研究计划项目摘要/摘要胃肠道癌遗传学（GICG）研究计划是一个基本的发现计划，翻译重点。 GICG计划的总体目标是发现遗传和表观遗传原因胃肠道癌，并将这些发现转化为新型治疗方法的发展和生物标志物用于早期检测，预防，诊断，诊断，预后和对GI药物反应的预测癌症。该程序围绕3个科学目的组织：（1）发现并在临床上翻译通用 GI癌的改变；（2）发现并在临床上翻译GI癌的表观遗传变化；（3）开发新的方法和模型，以促进基本和翻译的胃肠癌研究。目的反映了这些程序继续进行：i）在遗传和表观遗传原因中进行开创性的发现胃肠道癌和ii）通过将这些发现转化为新方法来实现重大临床影响癌症检测，预防和治疗，导致合并计划的工作组和计划与其他癌症中心调查人员的成员通过诠释媒介合作导致临床前和临床研究工作，赠款和试验方案。广泛使用一系列共享资源，尤其是基因组学，生物统计学和组织资源促进了会员的各个方面发现。在桑福德·马科维茨（共同领导）和郑（John）Wang（共同领导者）的领导下计划包括18个正式成员和3个副成员。成员代表11个部门，其中83％成员由64个项目资助，这些项目总计为550万美元的研究赠款资金（年度直接费用），其中510万美元经过同行评审，380万美元是NCI资助的。在2012年至2016年之间，GICG计划成员出版了534个出版物。癌症和与计划相关的出版物包括28％的间编程性，18％的截面性，涉及协作的8％和涉及合格的8％与另一个癌症中心。这个高效的计划使重大的练习改变了贡献使癌症患者受益。示例包括：i）正在进行的调查员发起的（并接受癌症 [SU2C]受支持）对PI3KCA突变CRC的新型靶向疗法的临床试验； ii）正在进行研究人员发射的针对Barret食管的生物标志物驱动检测的临床试验； iii）FDA批准和基于检测的甲基化DNA的商业采用CRC的粪便DNA筛选，一种方法由GICG研究人员开创性，并继续进行了正在进行的研究人员发起的临床试验； iv）验证两个标志性的流行病学队列 - 护士健康研究和卫生专业人员随访研究 - 通过阿司匹林对结肠癌化学预防的敏感性或抗性的预测生物标志物的发现；和v）NCI下一个临床开发计划的采用率是15-PGDH的小分子抑制剂由GICG调查人员发明。