Abstract
Breast cancer is the most common cancer in women worldwide, and the development of new technologies for better understanding of the molecular changes involved in breast cancer progression is essential. Metabolic changes precede overt phenotypic changes, because cellular regulation ultimately affects the use of small-molecule substrates for cell division, growth or environmental changes such as hypoxia. Differences in metabolism between normal cells and cancer cells have been identified. Because small alterations in enzyme concentrations or activities can cause large changes in overall metabolite levels, the metabolome can be regarded as the amplified output of a biological system. The metabolome coverage in human breast cancer tissues can be maximized by combining different technologies for metabolic profiling. Researchers are investigating alterations in the steady state concentrations of metabolites that reflect amplified changes in genetic control of metabolism. Metabolomic results can be used to classify breast cancer on the basis of tumor biology, to identify new prognostic and predictive markers and to discover new targets for future therapeutic interventions. Here, we examine recent results, including those from the European FP7 project METAcancer consortium, that show that integrated metabolomic analyses can provide information on the stage, subtype and grade of breast tumors and give mechanistic insights. We predict an intensified use of metabolomic screens in clinical and preclinical studies focusing on the onset and progression of tumor development.
Highlights
Breast cancer is the most common cancer in women worldwide, with an incidence of more than 410,000 new cases per year in the USA, Europe and Japan
Genetic alterations have been extensively characterized in breast cancer, we are just beginning to understand the changes in metabolism [2,3] that occur downstream of genomic and proteomic alterations in different types of breast tumors
This project aimed at characterizing the metabolism of breast cancer to identify new biomarkers and new targets for therapeutic interventions, and we compare these findings with results from other groups working in this area
Summary
Breast cancer is the most common cancer in women worldwide, with an incidence of more than 410,000 new cases per year in the USA, Europe and Japan. We examine results from the European FP7 METAcancer project, which combined the three major technologies for metabolic profiling (GCMS, LC-MS and NMR) to maximize metabolite coverage (Figure 1) This project aimed at characterizing the metabolism of breast cancer to identify new biomarkers and new targets for therapeutic interventions, and we compare these findings with results from other groups working in this area. Otto Warburg made the seminal observation [13] that glucose usage in tumors does not lead to production of excess NADH for subsequent oxidative phos phorylation in mitochondria for production of ATP, but instead lactate accumulates, even when enough oxygen is present for mitochondrial respiration Despite this seemingly less efficient use of glycolysis, large amounts of glucose are taken up by tumor cells. Numerous studies have noted alterations in choline metabolism during cancer cell metabolism, and these metabolites have been used for classifying tumor types [23,24] during the
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