Spatial metabolomics principles and application to cancer research

Mass spectrometry imaging (MSI) is an emerging technology in cancer metabolomics. Desorption electrospray ionization (DESI) and matrix-assisted laser desorption ionization (MALDI) MSI are complementary techniques to identify hundreds of metabolites in space with close to single-cell resolution. This technology leap enables research focusing on tumor heterogeneity, cancer cell plasticity, and the communication signals between cancer and stromal cells in the tumor microenvironment (TME). Currently, unprecedented knowledge is generated using spatial metabolomics in fundamental cancer research. Yet, also translational applications are emerging, including the assessment of spatial drug distribution in organs and tumors. Moreover, clinical research investigates the use of spatial metabolomics as a rapid pathology tool during cancer surgeries. Here, we summarize MSI applications, the knowledge gained by this technology in space, future directions, and developments needed. •Identification and quantification of metabolites by mass spectrometry imaging.•Infusion of 13C-labeled stable isotopes: challenges and achievements.•MALDI- and DESI-MSI in metabolomics cancer research.•Using MSI for translational and clinical applications.