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.

Public Health Relevance

Disparity exists between African-American and European-American women, in the clinical outcome of Triple Negative Breast Cancer. At present, the biological mechanisms, underlying the disparity are not well defined. The information gleaned from this proposal could rapidly revolutionize current prognostic and therapeutic approaches by revealing the biological underpinnings associated with Triple Negative Breast Cancer Disparity.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Spalholz, Barbara A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Baylor College of Medicine
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Ballester, Leomar Y; Lu, Guangrong; Zorofchian, Soheil et al. (2018) Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors. Acta Neuropathol Commun 6:85
Mishra, Prachi; Tang, Wei; Putluri, Vasanta et al. (2018) ADHFE1 is a breast cancer oncogene and induces metabolic reprogramming. J Clin Invest 128:323-340
Dai, Chen; Arceo, Jennifer; Arnold, James et al. (2018) Metabolomics of oncogene-specific metabolic reprogramming during breast cancer. Cancer Metab 6:5
Tian, Lin; Goldstein, Amit; Wang, Hai et al. (2017) Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming. Nature 544:250-254
Noonepalle, Satish K; Gu, Franklin; Lee, Eun-Joon et al. (2017) Promoter Methylation Modulates Indoleamine 2,3-Dioxygenase 1 Induction by Activated T Cells in Human Breast Cancers. Cancer Immunol Res 5:330-344
von Rundstedt, Friedrich-Carl; Rajapakshe, Kimal; Ma, Jing et al. (2016) Integrative Pathway Analysis of Metabolic Signature in Bladder Cancer: A Linkage to The Cancer Genome Atlas Project and Prediction of Survival. J Urol 195:1911-9
Park, Jun Hyoung; Vithayathil, Sajna; Kumar, Santosh et al. (2016) Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer. Cell Rep 14:2154-2165
Arnold, James M; Choi, William T; Sreekumar, Arun et al. (2015) Analytical strategies for studying stem cell metabolism. Front Biol (Beijing) 10:141-153
Bhowmik, Salil Kumar; Ramirez-Peña, Esmeralda; Arnold, James Michael et al. (2015) EMT-induced metabolite signature identifies poor clinical outcome. Oncotarget 6:42651-60
Lloyd, Stacy M; Arnold, James; Sreekumar, Arun (2015) Metabolomic profiling of hormone-dependent cancers: a bird's eye view. Trends Endocrinol Metab 26:477-85

Showing the most recent 10 out of 11 publications