Metabolomics in cancer research and emerging applications in clinical oncology

Abstract

Cancer has myriad effects on metabolism that include both rewiring of intracellular metabolism to enable cancer cells to proliferate inappropriately and adapt to the tumor microenvironment, and changes in normal tissue metabolism. With the recognition that fluorodeoxyglucose-positron emission tomography imaging is an important tool for the management of many cancers, other metabolites in biological samples have been in the spotlight for cancer diagnosis, monitoring, and therapy. Metabolomics is the global analysis of small molecule metabolites that like other -omics technologies can provide critical information about the cancer state that are otherwise not apparent. Here, the authors review how cancer and cancer therapies interact with metabolism at the cellular and systemic levels. An overview of metabolomics is provided with a focus on currently available technologies and how they have been applied in the clinical and translational research setting. The authors also discuss how metabolomics could be further leveraged in the future to improve the management of patients with cancer.

Keywords: cancer; intracellular; metabolism; metabolomics.

© 2021 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.

Figures

Figure 1.

Cancer and metabolism interact at many levels. Cancer causes metabolic alterations in cancer cells and normal tissues which in turn interact with intrinsic and extrinsic factors to affect systemic metabolism. Metabolomics is a systems based approach used to define these complex metabolic interactions for diagnostic and therapeutic gain. See text for details.

Figure 2.

The relationship between ”-omics” approaches of systems biology. Cancer is caused by changes at the genomic level that result in altered RNA transcription, protein expression, and protein function. The metabolome provides a functional readout of these upstream changes. In turn, individual metabolites affect protein activity and thereby alter RNA transcription and DNA replication.

Figure 3.

The optimal metabolomics workflow depends on source material and application. Various technologies and methods can be used to acquire raw data, which then provides the starting point for computational analysis. See text for details. MRSI magnetic resonance spectral imaging, GC gas chromatography, LC liquid chromatography, CE capillary electrophoresis, MS mass spectrometry, NMR nuclear magnetic resonance, MALDI-MSI matrix-assisted laser desorption/ionization mass spectrometric imaging.