Advancing METASPACE and Spatial Metabolomics for Cancer Research

SUMMARY Spatial omics are revolutionizing cancer biology by uncovering the intricate molecular architecture of tissues and solid tumors. They provide unprecedented insights into the tumor microenvironment, cell-cell heterogeneity, and interactions, helping map in situ cancer-associated cellular reprogramming. Additionally, spatial omics complement traditional histology techniques, adding novel molecular layers to the interrogation of solid tumors. Metabolism has re-emerged as a key factor in cancer and cancer therapy. While metabolic reprogramming, and particularly the Warburg effect, have been traditionally recognized as cancer hallmarks, recent developments reveal the regulatory roles of metabolites and their functional impacts on cancer cells, immune cells, and other contributors to the tumor microenvironment. Addressing the need for spatial biology and understanding metabolism of cancer in situ, spatial metabolomics was established as a technology able to detect metabolite abundances in tissues at near-single-cell resolution. Cancer biology is a key application of spatial metabolomics, as evidenced by numerous publications and grants in this field. It has provided insights into multiple applications in cancer research, including mapping metabolism of the solid tumor microenvironment at near-single-cell resolution, resolving metabolism of cancer cells and other cell types, conducting drug disposition studies for bioactive drug metabolites, correlating metabolic responses to detected drugs and metabolites in a dose- dependent manner, and performing molecular histology. Spatial metabolomics, commonly performed using imaging mass spectrometry, generates large and complex datasets, making data analysis critical for interpreting the data in cancer research and translating findings into actionable insights. To address this challenge, we previously developed METASPACE, a free and open-source cloud software platform for spatial metabolomics. METASPACE addresses a key problem in the field—metabolite identification—and provides a broad spectrum of features for experiment planning, quality control, data visualization, analysis, management, and sharing. The overarching goal of this project is to advance METASPACE, increase its utility, and accelerate the adoption and impact of spatial metabolomics in cancer research.