Metabolomics and metabolites in cancer diagnosis and treatment

Abstract Cancer is a leading cause of death worldwide. Metabolic reprogramming in cancers plays an important role in tumor initiation, malignant progression and therapeutic response. Based on this, significant progress has been made in the development of the metabolite-based early cancer detection and targeted interventions. Over the past decade, metabolomics has been widely applied to detect metabolic alterations in tumor cells as well as their microenvironment. However, an up-to-date systematic review to summarize the current metabolomic and metabolites in cancer, especially their connections to cancer diagnostics/prognostic biomarkers and therapeutic strategies, is lacking. Here, we first introduced the platforms and analytical processes of metabolomics, as well as their application in different biological matrix of tumor patients. Then, we summarized representative cancer studies in which specific metabolites was found to be act as diagnostic or prognostic/stratification biomarkers. Furthermore, we reviewed the current therapeutic strategies targeting cancer metabolism, particularly the drugs/compounds that are either market-approved or in clinical trials, and also analyzed the potential of metabolites in personalizing precision treatment. Finally, we discussed the key challenges in this field, including the technical limitations of metabolomics and the clinical limitations of therapeutic targeting cancer metabolism, and further explored the future directions such as multi-omics perspective and lifestyle interventions. Taken together, we provides a comprehensive overview from technological platforms of metabolomics to translational applications of metabolites, facilitating the discovery of novel biomarkers and targeting strategies for precision oncology.