Metabolic vulnerability of breast tumor cells during bone metastasis formation

Breast tumor-derived bone metastases cause severe morbidity and remain a therapeutic challenge as current therapies do not cure. Breast tumor cells often spread to bone before the primary tumor is treated, but they are not detected at that time. Insight in the early stages of bone metastasis is therefore necessary. Based on our data, we postulate that the metabolic profile of breast tumor cells promotes their survival and proliferation in bone. More precisely, availability of nutrients within the bone microenvironment and metabolic communication with osteoblasts will allow breast tumor cells with a compatible metabolic profile to grow in bone. To test this hypothesis, we will use transcriptomics and metabolomics on bone metastases in mouse models combined with metabolomics on in vitro co-cultures of tumor and skeletal cells. Using integrated bioinformatics, we will select interesting metabolic pathways, confirm their contribution to bone metastasis formation by genetic approaches in mouse models and validate the clinical relevance by a retrospective clinical study. These novel insights may lead to diagnostic or druggable targets.