To metabolomics and beyond:a technological portfolio to investigate cancer metabolism

Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression,metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosyntheticand redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field hasseen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell ora tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinicalapplications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the fieldenabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, theupgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellularresolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent offunctional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and noveltherapeutic targets that in concert with other technologies allow patient stratification and identification of new treatmentregimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emergingtechnologies, emphasizing advantages, disadvantages and applications with the potential of leading the development ofinnovative anti-cancer therapies.