Molecular and Cellular Oncology Program

摘要 概述和目标：分子和细胞肿瘤学(MCO)计划的目标是深入开展 追求可应用于有效癌症的关键基础科学知识的机制研究 预防、诊断和治疗。计划成员的专业知识广泛而深入，具有主要优势 在基因组不稳定、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，以及阐明与癌症相关的分子结构。研究要点：从板凳到板凳 床边团队的科学发现了白血病干细胞的代谢脆弱性，并为一种新的 Bcl-2抑制剂文奈德联合标准化疗产生的深度和耐受性 缓解(癌细胞，2018[1，2]；自然医学，2018[3])和添加自噬抑制剂的发现 氯喹到BRAF抑制剂维莫拉非尼降低了脑癌患者对抑制剂的耐药性(eLife，2017[4]； PNAS，2018[5])。计划活动：为实现其目标，MCO联合领导人使用由 科罗拉多大学癌症中心(UCCC)鼓励和支持计划内和计划间 通过组织年度务虚会和技术论坛进行协作，并促进跨学科 合作。在UCCC的支持下，共同领导人通过 创建和扩大共享资源(SR)，提供使用这些技术的试点资金，同时 利用合作机构的资源和研究优势。通过协调跨学科 MCO成员和翻译/临床研究计划之间的合作，在 MCO从工作台转移到临床前研究和临床试验，最终改善诊断， 癌症的治疗和预防。会员：该计划有56名正式会员和13名指导会员，费用为470万美元 NCI和900万美元的其他癌症同行评议研究资金。成员来自13个基础科学和临床 UCAMC、UCB、CSU和国家犹太人健康(NJH)的部门。自2016年7月以来，MCO成员 出版了476份以癌症为重点的出版物，其中245份(51%)要么是方案间的(45%)，要么是方案内的 程序性(17%)，或两者兼而有之(11%)；(27%)在期刊上使用IF≥10；130(27%)代表 与其他NCI癌症中心的研究人员合作。未来方向：通过静修/论坛、种子 赠款，以及相关工作人员代表的支持，MCO计划加强目前在交叉研究方面的优势 主题是癌症与新陈代谢、癌症与衰老。促进合作翻译研究 与集水区相关，MCO成员正在与UCCC社区外联办公室和 参与从科罗拉多州癌症相关个性化医学中心挖掘患者数据库 科罗拉多州服务不足人群的基因组信息。调查结果将与MCO成员共享，以 刺激与集水区相关的癌症研究。这些努力将推进基础癌症的发现 过程及其转化为更好的癌症预防和治疗。

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.