Center on the Physics of Cancer Metabolism

癌症代谢物理中心

• 批准号: 9339628
• 负责人: LEWIS C. CANTLEY
• 金额: $ 198.58万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-29 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9339628
• 关键词: Academia; Address; Affect; American; Biogenesis; Biological; Biology; Biophysics; Breast Cancer Patient; Breast Cancer Treatment; California; Cancer Biology; Cancer Center; Cancer Etiology; Cancer Patient; Caring; Cells; Cessation of life; Clinical; Computer Simulation; Consequentialism; Cues; Development; Disease; Education and Outreach; Engineering; Fostering; Funding; Generations; Genes; Glutamine; Goals; Government; Image; Image Analysis; Individual; Industry; Institution; Link; Malignant Neoplasms; Malignant neoplasm of pancreas; Mechanics; Medicine; Memorial Sloan-Kettering Cancer Center; Metabolic; Metabolic stress; Metabolism; Metastatic Prostate Cancer; Microfabrication; Modeling; NCI-Designated Cancer Center; Normal Cell; Obesity; Outcome; Oxidative Phosphorylation; Oxygen; Pathway interactions; Patient Care; Patients; Physical environment; Physics; Physiological; Property; Research Activity; Research Personnel; Research Project Grants; Research Training; Resource Sharing; Role; San Francisco; Scientist; Signal Pathway; Signal Transduction; Sum; Survivors; Testing; Therapeutic; Tissue Engineering; Tissues; Training; Tumor Cell Invasion; Tumor Cell Migration; Universities; Warburg Effect; Woman; Work; addiction; aerobic glycolysis; anticancer research; biological adaptation to stress; cancer subtypes; cancer therapy; clinical care; improved; insight; interdisciplinary approach; malignant breast neoplasm; microvesicles; nanoscale; neoplastic cell; next generation; novel therapeutic intervention; oncology; outcome forecast; patient advocacy group; physical property; physical science; precision medicine; prevent; programs; response; solute; synergism; therapeutic target; translational impact; triple-negative invasive breast carcinoma; tumor; tumor metabolism

Project Summary – Center on the Physics of Cancer Metabolism Despite advances in breast cancer treatment, metastatic disease remains incurable and is of particular concern in patients with triple negative breast cancer (TNBC). Both aberrant metabolic signaling and physical properties of the microenvironment have been independently defined as hallmarks of cancers, and limited experimental evidence suggests that they may be functionally linked. However, the current of lack of physiologically relevant culture models that capture relevant physical details prevents studying the specific mechanisms that link metabolic reprogramming, the physical microenvironment, and clinical outcomes of malignancy. By leveraging capabilities of six different institutions (Cornell University Ithaca, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, Purdue University, University of California San Francisco) the proposed Physical Sciences Oncology Center (PSOC) will apply physical science approaches to interrogate the multiscale biological and physical (structural, mechanical, and solute transport) mechanisms regulating tumor metabolism and function, as well as the consequences on tumor development, metastatic progression, and therapy response. This work will be addressed using three research projects that test the physical mechanisms by which the microenvironment regulates tumor metabolism and how obesity affects this interplay (Project 1), investigate the role of altered metabolism and the physical microenvironment in modulating the biogenesis and function of microvesicles (Project 2), and evaluate the integrated effects of physical and metabolic constraints on tumor cell migration and invasion (Project 3). These projects will be supported by two Cores that will provide computational modeling and microfabricated, patient-derived culture platforms with physiologically relevant metabolic stresses, mechanical cues, and transport phenomena (Core 1: Tissue Microfabrication Core) and will assist investigators in state-of-the-art imaging analysis of cellular metabolic state, microvesicle characterization, and nanoscale cellular properties (Core 2: Biophysics and Imaging Core). The research activities of our Center will be enhanced by an Education and Outreach Unit that will train interdisciplinary cancer researchers who are able to effectively engage across multiple sectors (academia, industry, government) to move treatment forward. All activities will be coordinated through an Administrative Core that will foster synergy and integration within the Center and with the overall Physical Sciences Oncology Network (PSON). Collectively, our proposed PSOC will generate physical sciences-driven mechanistic insights in the context of precision medicine approaches with the ultimate promise of improving clinical outcomes. While our initial focus will be on TNBC, it is our long-term goal to test the broad applicability of our findings to other subtypes of cancer as well as metastatic prostate cancer and pancreatic cancer thus, further advancing the overall impact of our Center.

癌症代谢物理中心（Center on the Physics of Cancer Metabolism） 尽管乳腺癌治疗取得了进展，但转移性疾病仍然是不可治愈的， 三阴性乳腺癌（TNBC）患者的关注。异常的代谢信号和身体 微环境的特性已经被独立地定义为癌症的标志， 实验证据表明，它们可能在功能上是相关的。然而，目前缺乏 生理相关的文化模型，捕捉相关的物理细节，防止研究的具体 将代谢重编程，物理微环境和临床结果联系起来的机制 恶性肿瘤通过利用六个不同机构的能力（康奈尔大学伊萨卡，威尔康奈尔 医学，纪念斯隆凯特琳癌症中心，MD安德森癌症中心，普渡大学， 加州圣弗朗西斯科大学）拟建的物理科学肿瘤学中心（PSOC）将 应用物理科学方法来询问多尺度生物和物理（结构， 机械和溶质转运）调节肿瘤代谢和功能的机制，以及 对肿瘤发展、转移进展和治疗反应的影响。这项工作将 使用三个研究项目来解决，这些项目测试了微环境的物理机制， 调节肿瘤代谢和肥胖如何影响这种相互作用（项目1），研究改变的作用。 代谢和物理微环境调节微泡的生物发生和功能 （项目2），并评估物理和代谢约束对肿瘤细胞迁移的综合影响 入侵（项目3）。这些项目将得到两个核心的支持， 具有生理学相关代谢的建模和微制造的患者来源的培养平台 应力、机械提示和运输现象（核心1：组织微加工核心），并将有助于 研究人员在国家的最先进的成像分析细胞代谢状态，微泡表征， 纳米细胞特性（核心2：生物物理学和成像核心）。我们中心的研究活动 将通过一个教育和推广单位来加强，该单位将培训跨学科的癌症研究人员， 能够有效地与多个部门（学术界、工业界、政府）合作， 性新所有活动将通过一个行政核心协调，以促进协同作用， 中心内部以及与整个物理科学肿瘤学网络（PSON）的整合。总的来说， 我们提出的PSOC将在精确度的背景下产生物理科学驱动的机制见解 医学方法的最终承诺是改善临床结果。虽然我们最初的重点将是 我们的长期目标是测试我们的发现对其他癌症亚型的广泛适用性 转移性前列腺癌和胰腺癌，从而进一步推进我们中心的整体影响。