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传导和代谢网络， 尖端的化学生物学，以更有效地靶向癌症中的限速途径，并将这些 通过改进的疗法或更好的生物标志物，为临床提供见解。为应对这些挑战，建行已 招募了多名新的世界级研究人员，他们对现有的卓越领域进行了重要补充， 促进高质量的合作研究。由Alec Kimmelman MD，PhD共同领导，最近被聘为主席 和Michele Pagano医学博士，HHMI生物化学和分子药理学主席 调查员，并在PCC的前生长控制计划主任，CCB是一个多学科的团队，49 来自纽约大学医学院（NYUSoM）和纽约大学15个系的会员和3名准会员 化学系，进行基础，转化和临床研究。这个高度重组的 该计划保留了前生长控制和干细胞计划的精选成员， 来自前乳房和GU计划的成员，并有一个实质性的重新集中的议程。研究是 现围绕三个相辅相成的主题目标组织：目标1）确定关键的监管机制， 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 代谢在癌症中被重新编程并发现新的代谢脆弱性;目的3）使用结构， 化学、蛋白质工程和药理学方法来靶向癌细胞依赖性， 治疗益处。项目成员拥有超过1720万美元的癌症相关资金，包括630万美元的NCI赠款， 810万美元的其他同行评审资金和280万美元的非同行评审支持。成员高度 富有成效和协作精神。在此资助期间，我们发表了604篇论文，其中许多是高影响力的 期刊，其中11%为计划内期刊，32%为计划间期刊，27%为机构间期刊（NCI-CC） 出版物。CCB为我们对信号传导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，发现新的分子靶点，并设计， 开发和/或测试了新的治疗方法，并阐明了其机制， 行动或抵抗。CCB通过以下方式促进PCC的使命：（1）产生创新的，高影响力的科学， 揭示癌细胞及其微环境中的新治疗靶点;（2）发现新的癌症药物 候选分子;（3）使患者参与高影响力，高内容的临床试验;以及（4）开发 通过新的PCC生物制品倡议， 开发代谢组学共享资源。特别关注影响我们流域的癌症 癌症领域（肺癌、胰腺癌、三阴性乳腺癌和前列腺癌）， 到翻译和丰富的长凳-床边-长凳活动组合。

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.