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

Abstract

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.

Explore & actuate: the future of personalized medicine in oncology through emerging technologies

“…A new kid on the block is COMPLETE-seq, enabling the identification of repeat-specific transcriptome from blood plasma, useful in differentiating cancer versus normal samples [26 && ]. Newer proteomic/metabolomic technologies generally utilize mass spectrometric methods such as imaging mass spectrometry (IMS) to reveal the heterogeneity of the TME, mainly through identifying and characterizing metabolomic reprogramming, a key component of cancer progression and drug resistance [27]. High mass-resolution imaging mass spectrometry (HMR-IMS) has recently shown the potential to delineate gastric cancer subtype-specific drug sensitivity with the help of unsupervised learning models, which is a substantial addition to the existing molecular platforms [28].…”

Immunological Aspects of Cancer Cell Metabolism

“…To pursue personalized medicine, developing comprehensive metabolic profiles for individual tumors could predict immune responsiveness and tailor treatments accordingly. Novel technologies, such as metabolomics and proteomics, would provide valuable insights into the metabolic status of cancer cells and their influence on the immune environment [82,83]. Further, advanced imaging and analytical techniques could lead us understand the metabolic gradients within the tumor microenvironment [84].…”

Metabolomics of natural samples: A tutorial review on the latest technologies

“…The Human Metabolome Database (HMDB) is a freely available, comprehensive database of small molecule metabolites found in the human body. It contains information on over 220,000 metabolites, including their chemical structures, physical properties, biological functions, and associated pathways [48]. HMDB also offers spectral data, allowing researchers to compare and identify metabolites using MS or nuclear magnetic resonance spectroscopy [49].…”