Abstract
PURPOSE: Breast cancer is a heterogeneous disease with several subtypes that currently do not have targeted therapeutic options. Metabolomics has the potential to uncover novel targeted treatment strategies by identifying metabolic pathways required for cancer cells to survive and proliferate. METHODS: The metabolic profiles of two histologically distinct breast cancer subtypes from a MMTV-Myc mouse model, epithelial-mesenchymal-transition (EMT) and papillary, were investigated using mass spectrometry-based metabolomics methods. Based on metabolic profiles, drugs most likely to be effective against each subtype were selected and tested. RESULTS: We found that the EMT and papillary subtypes display different metabolic preferences. Compared to the papillary subtype, the EMT subtype exhibited increased glutathione and TCA cycle metabolism, while the papillary subtype exhibited increased nucleotide biosynthesis compared to the EMT subtype. Targeting these distinct metabolic pathways effectively inhibited cancer cell proliferation in a subtype-specific manner. CONCLUSIONS: Our results demonstrate the feasibility of metabolic profiling to develop novel personalized therapy strategies for different subtypes of breast cancer. Schematic overview of the experimental design for drug selection based on breast cancer subtype-specific metabolism. The epithelial mesenchymal transition (EMT) and papillary tumors are histologically distinct mouse mammary tumor subtypes from the MMTV-Myc mouse model. Cell lines derived from tumors can be used to determine metabolic pathways that can be used to select drug candidates for each subtype.