Molecular and Cellular Oncology Program

分子和细胞肿瘤学项目

基本信息

批准号：
10332912
负责人：
RICHARD D SCHULICK
金额：
$ 5.62万
依托单位：
UNIVERSITY OF COLORADO DENVER
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：
1997-04-04 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10332912
关键词：
Adult Aging Aneuploidy Animal Model Automobile Driving Autophagocytosis BCL2 gene BRAF gene Basic Science Bioinformatics Biological Sciences Biometry Biotechnology CRISPR screen Cancer Center Cancer Center Support Grant Cancer Patient Catchment Area Cells Cellular biology Chloroquine Chromatin Remodeling Factor Clinical Clinical Research Clinical Trials Collaborations Colorado Combined Modality Therapy Communities Community Outreach Copy Number Polymorphism Custom DNA Damage DNA Repair DNA amplification Databases Dependence Development Diagnosis Disease Disease remission Down Syndrome Drug resistance Epigenetic Process Equilibrium Flow Cytometry Fostering Funding Future Gene Expression Genes Genetic Models Genetic Screening Genetic Transcription Genetic study Genomic Instability Genomics Goals Grant Guide RNA Head and neck structure Health Hematologic Neoplasms Histone Deacetylase Inhibitor Individual Institutes Institution Investigation Jordan Journals Knowledge Leadership Lung MAP Kinase Gene MAPK Signaling Pathway Pathway MDM2 gene Malignant Neoplasms Malignant neoplasm of brain Mediator of activation protein Medical Medicine Mentors Metabolic Metabolism Mission Molecular Molecular Structure Mutation Nature Pathology Patients Peer Review Predisposition Process Proteins Publications Publishing RNA RNA Processing RNA library Radiation-Sensitizing Agents Research Research Peer Review Research Personnel Resistance Resource Sharing Resources Science Seeds Signal Transduction Site TP53 gene Technology Telomerase Telomere Pathway Testing The University of Colorado Cancer Center Therapeutic Time Training Training Programs Translating Translational Research Translations Underserved Population Universities Woman anticancer research bench to bedside cancer cell cancer diagnosis cancer genome cancer prevention cancer therapy career development cellular oncology chemotherapy community engagement design epigenetic regulation experience experimental study follower of religion Jewish functional genomics fundamental research genome integrity improved inhibitor insight interdisciplinary collaboration kinase inhibitor leukemic stem cell malignant breast neoplasm member molecular oncology new combination therapies new technology novel novel diagnostics novel therapeutic intervention novel therapeutics oncology program personalized medicine pre-clinical prognostic value programs promoter response structural biology telomere tumor metabolism tumor progression

项目摘要

ABSTRACT Overview and Goals: The goal of the Molecular and Cellular Oncology (MCO) program is to perform in-depth mechanistic studies in pursuit of critical basic science knowledge that can be applied towards effective cancer prevention, diagnosis, and treatment. The expertise of program members is broad and deep, with major strengths in genome instability, gene expression and epigenetic regulation, DNA damage responses, telomeres, pathways controlling cell fate, and elucidation of cancer-relevant molecular structures. Research Highlights: Bench-to- bedside team science uncovered metabolic vulnerabilities of leukemia stem cells and contributed to a new therapy combination of BCL-2 inhibitor Venetoclax with standard chemotherapy that produces deep and durable remissions (Cancer Cell, 2018 [1,2]; Nature Medicine, 2018 [3]) and the finding that adding autophagy inhibitor chloroquine to BRAF inhibitor vemurafenib reduced inhibitor resistance for brain cancer patients (Elife, 2017 [4]; PNAS, 2018 [5]). Program Activities: To accomplish its goals, MCO co-leaders employ resources provided by the University of Colorado Cancer Center (UCCC) to encourage and enable intra- and inter-programmatic collaborations through organization of annual retreats and technology forums as well as fostering transdisciplinary collaborations. Assisted by UCCC support, the co-leaders catalyze new research by MCO members through the creation and expansion of Shared Resources (SR), by providing pilot funding to use these technologies, while leveraging resources and research strengths of collaborating institutions. Through coordinated transdisciplinary collaborations between MCO members and translational/clinical research programs, the discoveries made in MCO move from bench to preclinical investigations and clinical trials, which ultimately improve diagnosis, treatment, and prevention of cancer. Members: The program has 56 full and 13 mentored members with $ 4.7M NCI and $9.0M of other cancer peer-reviewed research funding. Members are from 13 basic science and clinical departments at UCAMC, UCB, CSU and National Jewish Health (NJH). Since July 2016, MCO members published 476 cancer-focused publications, of which 245 (51%) were either inter-programmatic (45%), intra- programmatic (17%), or both (11%); (27%) were in journals with an IF ≥10; and 130 (27%) represented collaborations with investigators at other NCI cancer centers. Future Directions: Through retreats/forums, seed grants, and support of relevant SRs, MCO plans to enhance current strengths in the cross-cutting research themes cancer and metabolism and cancer and aging. To promote collaborative translational research of relevance to the catchment, MCO members are collaborating with the UCCC Office of Community Outreach and Engagement to mine patient databases from the Colorado Center for Personalized Medicine for cancer-relevant genomic information in underserved populations in Colorado. Findings will be shared with MCO members to stimulate catchment-relevant cancer research. These efforts will advance the discovery of basic cancer processes and their translation into improved cancer prevention and treatment.

抽象的概述和目标：分子和细胞肿瘤学 (MCO) 项目的目标是深入开展追求可应用于有效癌症治疗的关键基础科学知识的机制研究项目成员的专业知识广泛而深入，具有重大优势。基因组不稳定性、基因表达和表观遗传调控、DNA 损伤反应、端粒、通路控制细胞命运，并阐明癌症相关的分子结构。研究亮点：实验室研究。床边团队科学发现了白血病干细胞的代谢脆弱性，并促成了一种新的研究 BCL-2 抑制剂 Venetoclax 与标准化疗的组合疗法可产生深度和持久的效果缓解（Cancer Cell，2018 [1,2]；Nature Medicine，2018 [3]）以及添加自噬抑制剂的发现氯喹对 BRAF 抑制剂威罗非尼降低了脑癌患者的抑制剂耐药性（Elife，2017 [4]； PNAS，2018 [5]）计划活动：为了实现其目标，MCO 联合领导者利用以下机构提供的资源。科罗拉多大学癌症中心 (UCCC) 鼓励并支持项目内和项目间的项目通过组织年度务虚会和技术论坛以及促进跨学科合作在 UCCC 的支持下，联合领导者通过以下方式促进 MCO 成员的新研究。通过提供试点资金来使用这些技术来创建和扩展共享资源（SR），同时通过协调的跨学科，利用合作机构的资源和研究优势。 MCO 成员和转化/临床研究项目之间的合作， MCO 从实验室转向临床前研究和临床试验，最终改善诊断、成员：该计划有 56 名正式成员和 13 名指导成员，资金 470 万美元。 NCI 和其他 900 万美元的癌症同行评审研究资金成员来自 13 个基础科学和临床领域。 UCAMC、UCB、CSU 和国家犹太健康 (NJH) 部门自 2016 年 7 月起，MCO 成员。发表了 476 篇以癌症为主题的出版物，其中 245 篇 (51%) 是项目间出版物 (45%)、内部出版物程序化（17%），或两者兼而有之（11%）；（27%）发表在 IF ≥ 10 的期刊上，并且 130 篇（27%）与其他 NCI 癌症中心的研究人员合作未来方向：通过静修会/论坛、种子。拨款和相关 SR 的支持，MCO 计划增强当前跨领域研究的优势主题癌症与新陈代谢以及癌症与衰老。 MCO 成员正在与 UCCC 社区外展办公室合作，参与挖掘科罗拉多个性化医疗中心的癌症相关患者数据库科罗拉多州服务不足人群的基因组信息将与 MCO 成员共享。刺激与流域相关的癌症研究。这些努力将促进基础癌症的发现。过程及其转化为改进的癌症预防和治疗。