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Identifying factors regulating cancer metabolism in vivo

识别体内调节癌症代谢的因素

基本信息

批准号：
10657812
负责人：
Brandon Faubert
金额：
$ 24.9万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657812
关键词：
Address Affect Aggressive behavior Angiogenesis Inhibitors Behavior Biological Markers Biology Blood flow Cancer Cell Growth Cell Communication Cell Culture Techniques Cell Line Cells Clinical Clinical Oncology Consumption Cultured Cells Disease Educational process of instructing Experimental Models FOXM1 gene Functional disorder Glucose Grant Heterogeneity Histologic Human Immune Immune Evasion Immune response Immune system Immunocompetent In Vitro Infiltration Infusion procedures Intrinsic factor Knowledge Label Lung Lung Neoplasms Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of lung Measures Mentors Metabolic Metabolic Pathway Metabolic stress Metabolism Modeling Molecular Mus Mutation Nutrient Outcome Measure Pathway interactions Patient-Focused Outcomes Patients Perfusion Phase Phenotype Primary Neoplasm Reporting Research Role Sampling Testing Therapeutic Tissues Translating Tumor Tissue Work Xenograft procedure cancer imaging clinical imaging clinical translation imaging agent imaging modality in vivo insight mRNA Expression metabolic phenotype mouse model new therapeutic target novel novel therapeutics patient derived xenograft model pharmacologic preference protein expression response subcutaneous tumor tumor behavior tumor metabolism tumor progression uptake

项目摘要

Project Summary Altered metabolism is a hallmark of malignancy. Metabolic pathway changes contribute to cancer cell growth, transformation and survival. These differences can be exploited to image tumor tissue and provide predictive information to patients. Importantly, these metabolic differences can also be exploited therapeutically. Thus, understanding cancer metabolism has important implications for pathophysiology and clinical oncology. Progress in translating these studies into new therapies is limited by the fact that much of knowledge in tumor metabolism is derived from studies in cultured cells with unknown relevance to disease biology. Similarly, cell line xenografts may not accurately recapitulate the cellular heterogeneity of a primary tumor. For these reasons, little is known about tumor metabolism in vivo, and the factors that regulate this behavior. My proposal utilizes clinical samples wherein the metabolic behavior of the primary human tumor is evaluated and characterized. These tissues are translated to mouse models, where I will evaluate what metabolic phenotypes are retained, as well as test what intrinsic and extrinsic factors promote metabolic behavior. During the mentored phase of the grant, I will focus on identifying retained/intrinsic metabolic phenotypes, as well as extrinsic factors such as the role of tumor perfusion on nutrient preference. With these insights, I will continue independent research focusing on the molecular details of these factors, to identify combinations of factors influencing cancer metabolism in vivo.

项目摘要代谢改变是恶性肿瘤的标志。代谢途径的变化有助于癌细胞的生长，转型与生存这些差异可以用于对肿瘤组织进行成像，并提供预测性信息。给病人的信息。重要的是，这些代谢差异也可以用于治疗。因此，在本发明中，了解癌症代谢对病理生理学和临床肿瘤学具有重要意义。将这些研究转化为新疗法的进展受到以下事实的限制：代谢是从培养细胞的研究中获得的，与疾病生物学的相关性未知。同样，Cell 线异种移植物可能不能准确地概括原发性肿瘤的细胞异质性。基于这些理由，对体内肿瘤代谢以及调节这种行为的因素知之甚少。我的提议利用了临床样品，其中评价和表征所述原发性人肿瘤的代谢行为。将这些组织转化为小鼠模型，在那里我将评估保留了哪些代谢表型，以及测试哪些内在和外在因素促进代谢行为。在辅导阶段，授予，我将重点关注识别保留/内在代谢表型，以及外在因素，例如肿瘤灌注对营养偏好的作用。有了这些见解，我将继续独立研究重点，这些因素的分子细节，以确定影响癌症代谢的因素组合， vivo.