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

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SPRINGERNATURE
DOI: 10.1038/s41392-023-01380-0

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Tumour cells possess the ability to reprogram their metabolism in order to support tumor growth, progression, and resistance. This reprogramming involves significant changes in bioenergetic, biosynthetic, and redox status to meet the increased energetic demands of the cells. Recent advancements in biochemical technologies, such as metabolomics and fluxomics, have provided researchers with powerful tools to study cancer metabolism and gain a better understanding of its complex activities on both qualitative and mechanistic levels. Additionally, the development of single-cell analysis technologies and functional genomic screening have further enhanced our ability to investigate cancer biology, identify biomarkers, and discover new therapeutic targets and treatment strategies.
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, biosynthetic and redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field has seen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell or a tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinical applications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the field enabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, the upgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellular resolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent of functional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and novel therapeutic targets that in concert with other technologies allow patient stratification and identification of new treatment regimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emerging technologies, emphasizing advantages, disadvantages and applications with the potential of leading the development of innovative anti-cancer therapies.

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