Researchers from the National Centre for Genomic Analysis (CNAG), located at the Barcelona Science Park, and the University of Milano-Bicocca (Italy), in collaboration with Yale School of Medicine (USA), have developed a new computational tool capable of revealing a previously invisible layer of cancer: the metabolic strategies of its cells, which could promote proliferation, immune evasion, or tumour progression depending on their location within the tissue. The study has been published in the journal Systems Biology and Applications.

Tumours are made up of vast numbers of cells whose primary objective is to multiply while escaping the immune system. Each cell plays a specific role within this complex network, where the activity of their genes determines the function they perform. This genetic information has already transformed our understanding of cancer biology since the advent of high-resolution genomic technologies, and further advances came with spatial transcriptomics, which made it possible to pinpoint different tumour cell types and their patterns of gene expression directly within tissue.

This new tool enables researchers to map the metabolic strategies that underpin tumour growth and survival. “Our aim was to understand how a cell’s location within a tumour influences the way it acquires energy and nutrients. We already knew which genes were active in individual cells, so we asked ourselves: what if we could also map cell metabolism? In other words, we can aggregate their gene expression, to infer their metabolic activities such as cell growth, survival and spread”, explains Dr Davide Maspero, researcher at CNAG and first author of the study.

To address this question, the team developed the spatial Flux Balance Analysis (spFBA) method in collaboration with the University of Milano-Bicocca (Italy) and Yale School of Medicine (USA). Published in Systems Biology and Applications , a Nature Portfolio journal, the new computational framework enables, for the first time, the reconstruction of spatial metabolic patterns from spatial transcriptomics data, capturing both cancer cells and the surrounding tumour microenvironment.

The resulting maps reveal the metabolic reactions taking place across different tumour regions, or niches, showing which areas rely more heavily on glycolysis to generate energy, which show greater resources to biomass production for growth and cell division, and which consume or release lactate, a key molecule that cells can use both as an energy source and as a precursor for the synthesis of new cellular components. These metabolic profiles act as landmarks within the tumour, allowing researchers to infer the dominant biological activities in different regions and estimate their proliferative potential. The findings uncover the metabolic strategies tumour cells use to proliferate, and spread to other organs, opening the way to improved predictions of tumour evolution and the development of more targeted therapies.

First metabolic maps of colorectal and kidney cancer

Considering the metabolic plasticity of colorectal cancer, a characteristic that makes it one of the most aggressive tumour types because of its remarkable ability to adapt the way it acquires energy and nutrients, the researchers began by analysing samples from patients with colorectal cancer and liver metastases. Their goal was to gain a deeper understanding of the mechanisms that enable tumours to spread and colonise distant organs. The resulting metabolic maps revealed that certain tumour regions consumed lactate to generate energy and produce tumour biomass, whereas the surrounding non-tumour tissue, or stroma, primarily produced lactate. Taken together, the findings show how tumours establish a highly organised network of metabolic cooperation between different regions, with some producing nutrients that others consume, thereby supporting continued tumour growth.

In kidney cancer, spatial analysis using spFBA confirmed the widespread presence of tumour regions with high levels of lactate production, a pattern consistent with the Warburg phenotype. This phenomenon describes the tendency of cancer cells to preferentially generate energy by fermenting, glucose even when oxygen is available. However, the analysis also revealed that this behaviour is far from uniform across the tumour. While some regions continued to produce and secrete lactate despite the presence of oxygen, others displayed the metabolic profile typically associated with oxygen-poor environments, relying more heavily on anaerobic glycolysis. Once again, different parts of the tumour adopt distinct metabolic strategies to achieve the same outcome: sustaining disease progression.

Following these first metabolic maps, which highlight the crucial role of tumour spatial organisation in securing the resources required for continued growth, the researchers are already working on the next stage of the project. The team is developing a new version of the spFBA software that will be compatible with a broader range of spatial transcriptomics datasets, making it easier for research centres and healthcare institutions worldwide to incorporate this computational tool into their own analyses.

» Article of reference: Maspero, D., Marteletto, G., Lapi, F. et al. Spatial FBA reveals heterogeneous Warburg niches in renal tumors and lactate consumption in colorectal cancer. npj Syst Biol Appl 12, 32 (2026). https://doi.org/10.1038/s41540-026-00654-x

» Link to the news: CNAG website [+]