Cancer Metabolism and Signaling Networks

癌症代谢和信号网络

• 批准号: 10174824
• 负责人: Francesca M Marassi
• 金额: $ 4.8万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10174824
• 关键词: Address; Apoptosis; Area; Autophagocytosis; Biology; Cancer Cell Growth; Cancer Center Support Grant; Cancer Model; Cell Death; Cell Survival; Cells; Cellular Stress; Cessation of life; Chemicals; Collaborations; Data; Doctor of Philosophy; Drug Design; Educational workshop; Equilibrium; Event; Faculty; Fostering; Funding; Genomics; Goals; Grant; Heat shock proteins; Inflammation; Innovative Therapy; International; Joints; Knowledge; Lead; Libraries; Link; Malignant Neoplasms; Mentors; Metabolic; Metabolism; Molecular; Mus; Normal Cell; Nutrient; Oxygen; Paper; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Postdoctoral Fellow; Protein Biosynthesis; Publications; Publishing; Radiation; Research Personnel; Signal Pathway; Signal Transduction; Stress; Structure; Students; System; Translating; Translations; Work; X-Ray Crystallography; anticancer research; base; cancer cell; cancer therapy; chemotherapy; design; detection of nutrient; efficacious treatment; endoplasmic reticulum stress; expectation; high throughput screening; interdisciplinary approach; interest; meetings; member; metabolic abnormality assessment; multicatalytic endopeptidase complex; new therapeutic target; novel therapeutics; programs; protein degradation; recruit; response; therapeutic target; tumor; tumor metabolism; tumor microenvironment; uncontrolled cell growth; Address; Apoptosis; Area; Autophagocytosis; Biology; Cancer Cell Growth; Cancer Center Support Grant; Cancer Model; Cell Death; Cell Survival; Cells; Cellular Stress; Cessation of life; Chemicals; Collaborations; Data; Doctor of Philosophy; Drug Design; Educational workshop; Equilibrium; Event; Faculty; Fostering; Funding; Genomics; Goals; Grant; Heat shock proteins; Inflammation; Innovative Therapy; International; Joints; Knowledge; Lead; Libraries; Link; Malignant Neoplasms; Mentors; Metabolic; Metabolism; Molecular; Mus; Normal Cell; Nutrient; Oxygen; Paper; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacology; Postdoctoral Fellow; Protein Biosynthesis; Publications; Publishing; Radiation; Research Personnel; Signal Pathway; Signal Transduction; Stress; Structure; Students; System; Translating; Translations; Work; X-Ray Crystallography; anticancer research; base; cancer cell; cancer therapy; chemotherapy; design; detection of nutrient; efficacious treatment; endoplasmic reticulum stress; expectation; high throughput screening; interdisciplinary approach; interest; meetings; member; metabolic abnormality assessment; multicatalytic endopeptidase complex; new therapeutic target; novel therapeutics; programs; protein degradation; recruit; response; therapeutic target; tumor; tumor metabolism; tumor microenvironment; uncontrolled cell growth

ABSTRACT – CANCER METABOLISM AND SIGNALING NETWORKS PROGRAM The long-term goal of the Cancer Metabolism and Signaling Networks (CMSN) program is to unravel the mechanisms and signaling networks in normal and cancer cells that govern their ability to either survive or to undergo various forms of death when stressed (as a consequence of either the inherent requirements of uncontrolled cancer cell growth, or chemotherapy). The program includes 10 investigators, including 5 adjuncts, with strong expertise in autophagy and cell death, metabolic signaling, and structural and chemical biology, who work in a highly interactive approach with the ultimate goal of efficient translation of our discoveries into more selective and efficacious therapies. The program consists of three well-defined and highly synergistic themes: (1) Cancer Metabolism, (2) Nutrient Sensing, and (3) Cell Death and Survival. These themes are conceptually linked, with metabolic and protein stress in cancer cells closely interconnected to cell survival, cell death, and autophagy. Exploiting these and other signaling pathways through chemical biology is expected to lead to new therapies for cancer. The program has reinforced its cancer focus, as suggested by the previous review, and fosters collaborations among its members through joint lab meetings, monthly program meetings, retreats, and mentoring of junior faculty, postdoctoral fellows, and students. As documented by our current annual direct cancer-related funding of $7.3M with $4.6M from NCI (63%), the program has been very productive during this period. Program members currently lead or participate in a total of 28 grants including 19 R01s (11 from NCI), and multiple NExT (NCI) projects. Members have authored 254 cancer-relevant papers (between 2014 and 2019), of which 24% were collaborative (13% intra-programmatic and 11% inter-programmatic). Of these, 29 were published in 2018, 21% intra-programmatic and 7% inter-programmatic. A central goal for the program for the next five years is to further enhance interactions among members that allow us to address fundamental questions in the area of cancer metabolism and cell survival. We plan to extend our expertise in these areas by recruiting at least one faculty in cancer metabolism and, in collaboration with TMCI, another faculty with interest in metabolism in the tumor stroma, an emerging field at the interface of metabolism, inflammation, and the tumor microenvironment. Another faculty member will be recruited in the area of autophagy in mouse cancer models. Our ability to translate our findings into innovative therapies will benefit greatly from the presence of program members with outstanding expertise in structural and chemical biology and the rational design of drugs based on structural data, combined with the capabilities of the Conrad Prebys Center for Chemical Genomics in medicinal chemistry and high-throughput screening.

摘要 - 癌症代谢和信号网络计划 癌症代谢和信号网络（CMSN）计划的长期目标是揭开 正常和癌细胞中其生存能力或癌细胞中的机制和信号网络 压力时会经历各种形式的死亡（由于 不受控制的癌细胞生长或化疗）。该计划包括10位调查人员，包括5个辅助人员 在自噬和细胞死亡，代谢信号传导以及结构和化学生物学方面具有强大的专业知识，谁 以高度互动的方法进行工作，以有效地翻译我们的发现为最终目标 选择性有效的疗法。该计划由三个定义明确且高度协同的主题组成： （1）癌症代谢，（2）营养感应和（3）细胞死亡和生存。这些主题在概念上是 与细胞存活，细胞死亡和 自噬。通过化学生物学利用这些和其他信号通路将导致新的 癌症的疗法。如先前的评论所建议的那样，该计划加强了癌症的重点， 通过联合实验室会议，每月计划会议，务虚会和 指导初级教师，博士后研究员和学生。正如我们当前年度直接的记录 与癌症有关的资金为730万美元，NCI的460万美元（63％），该计划在此期间非常有生产力 时期。计划成员目前领导或参与总共28笔赠款，包括19 R01（来自NCI的11个）， 和多个下一个（NCI）项目。成员已经撰写了254张与癌症相关的论文（2014年至 2019年），其中24％是协作（13％的策略内，跨编程间的11％）。其中29 于2018年发表，前编程中有21％和7％的程序间媒介。该计划的中心目标 接下来的五年是进一步增强成员之间的互动，使我们能够解决基本 癌症代谢和细胞存活领域的问题。我们计划通过 至少招募一位癌症代谢的教师，并与TMCI合作，是另一个有兴趣的教师 在肿瘤基质中的代谢中，新陈代谢，炎症和肿瘤界面的新兴领域 微环境。在小鼠癌模型中，将在自噬领域招募另一位教职员工。 我们将发现转化为创新疗法的能力将从计划的存在中受益匪浅 具有出色的结构和化学生物学专业知识的成员以及基于药物的合理设计 关于结构数据，结合了Conrad Prebys化学基因组中心的能力 药物化学和高通量筛查。