Identifying Personalized Metabolic Signatures in Breast Cancer.

TitleIdentifying Personalized Metabolic Signatures in Breast Cancer.
Publication TypeJournal Article
Year of Publication2020
AuthorsBaloni P, Dinalankara W, Earls JC, Knijnenburg TA, Geman D, Marchionni L, Price ND
JournalMetabolites
Volume11
Issue1
Date Published2020 Dec 30
ISSN2218-1989
Abstract

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism, and reactive oxygen species (ROS) detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

DOI10.3390/metabo11010020
Alternate JournalMetabolites
PubMed ID33396819
PubMed Central IDPMC7823382
Grant ListR01CA200859 / NH / NIH HHS / United States
Related Faculty: 
Luigi Marchionni, M.D., Ph.D.

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