Cancer Cell Biology (CCB) Research Program

摘要 癌症细胞生物学计划(CCB)的使命是实现个性化癌症治疗的承诺 通过阐明控制癌细胞特性的关键信号和代谢网络，采用 更有效地针对癌症中的限速途径的尖端化学生物学，并将这些 通过改进的治疗方法或更好的生物标记物，为临床提供见解。为了应对这些挑战，建行已经 招募了多名新的世界级调查人员，他们对现有的卓越领域进行了关键的补充，并 促进高质量、协作性研究。由亚历克·金梅尔曼博士共同领导，最近被聘为主席 和HHMI生物化学和分子药理学主席Michele Pagano MD 建行是一支由49人组成的多学科团队，曾担任PCC增长控制项目的调查员和主任 来自纽约大学医学院(NYUSoM)和纽约大学15个系的成员和3名准成员 化学系，从事基础研究、转化研究和临床研究。这是一个高度重组的 计划保留了以前的生长控制和干细胞计划中的精选成员，合并了几个 来自前乳房和GU计划的成员，并有了实质性的重新关注的议程。研究是 现在围绕三个相辅相成的主题目标组织：目标1)确定关键的 在人类肿瘤中赋予选择性依赖性的癌症相关基因；目的2)描述如何 新陈代谢在癌症中被重新编程并发现新的新陈代谢脆弱性；目标3)使用结构性的， 针对癌细胞依赖性的化学、蛋白质工程和药理学方法 治疗效果。该计划成员有1720万美元的癌症相关资金，其中包括630万美元的NCI赠款， 810万美元的其他同行审查资金，以及280万美元的非同行审查支持。会员们高度重视 高效率和协作性。在这一资助期间，我们发表了604篇论文，其中许多是影响很大的论文 期刊，11%是方案内的，32%是方案间的，27%是机构间的(NCI-CC) 出版物。CCB为我们对信号和代谢的基本理解提供了关键的新见解 基因定义的癌症亚型的脆弱性，发现了新的分子靶点，并设计了， 在研究人员发起的试验(IITs)中开发和/或测试新的治疗方法，并阐明其机制 行动或抵抗。中国建设银行通过以下方式促进PCC使命：(1)产生创新、高影响力的科学 揭示癌细胞及其微环境的新治疗靶点；(2)发现抗癌新药 候选分子；(3)使患者参与高影响、高内容的临床试验；以及(4)开发 通过新的PCC生物制品倡议和个人调查人员无法获得的尖端技术 发展代谢组学共享资源。人们特别关注癌症对我们水源的影响。 领域(肺癌、胰腺癌、三阴性乳腺癌和前列腺癌)，坚定的承诺 到翻译和丰富的板凳床边活动组合。

ABSTRACT The mission of the Cancer Cell Biology Program (CCB) is to fulfill the promise of personalized cancer therapy by elucidating the critical signaling and metabolic networks controlling cancer cell properties, employing cutting-edge chemical biology to more effectively target rate-limiting pathways in cancer, and translating these insights to the clinic, via improved therapies or better biomarkers. To address these challenges, CCB has recruited multiple new, world-class investigators who critically complement existing areas of excellence and promote high quality, collaborative research. Co-led by Alec Kimmelman MD, PhD, recently recruited as Chair of Radiation Oncology, and Michele Pagano MD, Chair of Biochemistry and Molecular Pharmacology, HHMI investigator, and Director of the former Growth Control Program at PCC, CCB is a multi-disciplinary team of 49 members and 3 associate Members from 15 departments at NYU School of Medicine (NYUSoM) and the NYU Department of Chemistry, who perform basic, translational, and clinical research. This highly restructured program retains select members from the former Growth Control and Stem Cell programs, incorporates several members from the former Breast and GU programs, and has a substantially re-focused agenda. Research is now organized around three complementary thematic aims: Aim 1) To identify regulatory mechanisms for key cancer-relevant genes that confer selective dependencies in human tumors; Aim 2) To delineate how metabolism is reprogrammed in cancer and discover new metabolic vulnerabilities; Aim 3) To use structural, chemical, protein engineering and pharmacological approaches to target cancer cell dependencies for therapeutic benefit. Program members have >$17.2M in cancer-related funding, including $6.3M in NCI grants, $8.1M in other peer-reviewed funding, and $2.8M in non-peer reviewed support. Members are highly productive and collaborative. During this funding period, we published 604 papers, many in high-impact journals, with 11% intra-programmatic, 32% inter-programmatic and 27% inter-institutional (NCI-CC) publications. CCB contributed key new insights into our basic understanding of signaling and metabolic vulnerabilities in genetically defined cancer subtypes, uncovered new molecular targets, and designed, developed and/or tested new therapies in investigator-initiated trials (IITs) and elucidated their mechanism of action or resistance. CCB promotes the PCC mission by: (1) producing innovative, high-impact science that reveals new therapeutic targets in cancer cells and their microenvironment; (2) discovering new cancer drug molecule candidates; (3) accruing patients to high-impact, high-content clinical trials; and (4) developing sophisticated technologies beyond the reach of individual investigators via the new PCC Biologics Initiative and Developing Metabolomics shared resource. There is a particular focus on cancers impacting our catchment area (lung cancer, pancreas cancer, triple negative breast cancer and prostate cancer), a strong commitment to translation and a rich portfolio of bench-bedside-bench activities.