Metabolic Signatures of Human Breast Cancer

Abstract

Metabolomics has emerged as a new discovery tool with the promise of identifying therapeutic targets in cancer. Recent discoveries described essential metabolomic pathways in breast cancer and characterized oncometabolites that drive tumor growth and progression. Oncogenes like MYC and tumor suppressor genes like TP53 prominently affect breast cancer biology through regulation of cell metabolism and mitochondrial biogenesis. These findings indicate that tumors with dominant mutations could be susceptible to inhibitors of disease metabolism. Moreover, various pre-clinical and clinical studies have linked tumor metabolism to therapeutic response and patient survival. Thus, recent advances suggest that metabolic profiling provides new opportunities to improve outcomes in breast cancer. In this review, we have summarized some of the identified roles of oncometabolites in breast cancer biology and highlight their clinical utility.

Keywords: Cancer; biomarker; metabolism; prognosis; therapy.

Figure 1.

Examples of putative oncogenic metabolites (“oncometabolites”) in breast cancer. Increased availability and aberrant accumulation of these metabolites can enhance tumor growth and metastasis. Shown are functional classes of oncometabolites and how they affect breast cancer biology. Most metabolites are generated within breast tumors but some originate from distant organs and reach the breast tissue through the blood supply (e.g., 27-hydroxycholesterol, glutamine, deoxycholate, tryptophan). Deoxycholate has a microbial origin.

Figure 2.

Metabolic profiling to guide early detection, prognosis, and response to therapy. Various approaches are being applied to develop metabolite-based tests for early disease detection and stratification of patients for clinical management of the disease. LC-MS: liquid chromatography–mass spectrometry; GC-MS: gas chromatography–mass spectrometry; NMR: nuclear magnetic resonance spectroscopy.