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Delineating racially distinct metabolic pathways in triple negative breast cancer

描绘三阴性乳腺癌中种族不同的代谢途径

基本信息

批准号：
9120349
负责人：
Arun Sreekumar
金额：
$ 33.52万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9120349
关键词：
Acids African American Age Alanine American Arachidonic Acids Benign Biochemical Biochemical Pathway Bioinformatics Biological Biological Factors Biological Process Biometry Body Fluids Breast Breast Cancer Epidemiology Cancer Biology Cell Line Cells Cellular Metabolic Process Clinical Data Set Development Drug Targeting European Fatty Acids Fingerprint Future Gene Proteins Generations Genetic Genetic Predisposition to Disease Glean Goals Health In Vitro Incidence Inequality Inherited Knowledge Lipids Malignant - descriptor Malignant neoplasm of prostate Mammary Gland Parenchyma Mass Spectrum Analysis Measurement Measures Metabolic Metabolic Marker Metabolic Pathway Metabolism Methodology Mitochondria Modeling N-acetylaspartate Nature Outcome PTGS2 gene Pathology Pathway interactions Phospholipids Play Prognostic Marker Publishing Research Role Sarcosine Science Serum Staging Techniques Therapeutic Tissues Training Tryptophan Unsaturated Fatty Acids Woman Work arm base cancer health disparity cancer subtypes follow-up health care availability in vivo Model insight malignant breast neoplasm metabolic profile metabolome metabolomics multiple reaction monitoring outcome forecast prognostic racial disparity small molecule triple-negative invasive breast carcinoma tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): The long-term objective of our research plan is to reduce the disproportionate effects of Triple Negative Breast Cancer on African American women. A guiding principle of our methodology is metabolic differences exist between triple negative breast cancers of African American and European American origin and that these differences can explain, in part, breast cancer health disparity. In this application, we propose t use the technique of metabolomic measurements to uncover these underlying differences. Metabolomics describes the science of quantifying the levels of metabolites (e.g., small molecules) that are the byproducts of cellular metabolism. In other words, in this kind of analysis we are measuring the biochemical entities (or metabolites) that are produced by the functional machinery of the cell. With knowledge of the identity of specific metabolites we can infer the biological processes that produced them, thus gaining insight into a cell's metabolism. We have recently published the first study describing metabolic alterations associated with triple negative breast cancer in African-American women. We identified alterations in two key biochemical pathways namely those involved in metabolism of 2-hydroxyglutarate and arachidonic acid, both of which were elevated in a subset of African-American triple negative breast cancers having a poor clinical outcome. In this application we propose to follow up on these findings by 1) validating elevated levels of fatty acids (including arachidonic acid) and phospholipids in independent set of triple negative breast cancer tissues from African-American women 2) characterize the mechanisms causing accumulation of 2-hydroxyglutarate and arachidonic acid in African- American women and 3) develop a first-generation panel of prognostic metabolic markers for African-American women using metabolites in the 2-hydroxyglutarate and fatty acid pathway. At the conclusion of this study, we will have developed a racially derived metabolomic model for triple negative breast cancer as well as identified candidate pathways for future drug targeting.

描述（由申请人提供）：我们研究计划的长期目标是减少三阴性乳腺癌对非裔美国妇女的不成比例的影响。我们的方法的指导原则是非裔美国人和欧洲裔美国人起源的三阴性乳腺癌之间存在代谢差异，这些差异可以部分解释乳腺癌健康差异。在本申请中，我们建议使用代谢组学测量技术来揭示这些潜在的差异。代谢组学描述了定量代谢物水平的科学（例如，小分子），它们是细胞代谢的副产物。换句话说，在这种分析中，我们测量的是由细胞的功能机制产生的生化实体（或代谢物）。通过了解特定代谢物的身份，我们可以推断产生它们的生物过程，从而深入了解细胞的代谢。我们最近发表了第一项研究，描述了与三阴性相关的代谢改变。非裔美国女性的乳腺癌我们确定了两个关键生化途径的改变，即参与2-羟基戊二酸和花生四烯酸代谢的途径，这两种途径在临床结果较差的非裔美国人三阴性乳腺癌亚组中均升高。在本申请中，我们建议通过以下方式跟进这些发现：1）验证脂肪酸水平升高2）描述了在非裔美国妇女中引起2-羟基戊二酸和花生四烯酸积累的机制，3）开发了第一代非裔美国妇女预后代谢标志物组，使用2-羟基戊二酸和脂肪酸途径代谢物的美国女性。在这项研究的结论，我们将开发一个种族衍生的代谢组学模型的三阴性乳腺癌，以及确定候选途径，为未来的药物靶向。