An international research team led by the MRC Laboratory of Medical Sciences at Imperial College London and the University of Cologne has made a significant discovery regarding the role of tumor-associated microbes in cancer treatment. Their findings, published online in Cell Systems on September 10, 2025, indicate that certain bacteria associated with tumors can produce a molecule known as 2-methylisocitrate (2-MiCit), which has the potential to enhance the efficacy of chemotherapy.
Researchers conducted a large-scale screening with over 1,100 conditions using the microscopic worm C. elegans, identifying that the bacterium E. coli generates 2-MiCit. This molecule was found to improve the performance of the chemotherapy drug 5-fluorouracil (5-FU). Further investigations using human cancer cells and a fly model of colorectal cancer corroborated these findings, demonstrating that 2-MiCit possesses anti-cancer properties and can extend survival in the model organism.
The study's authors explain that 2-MiCit disrupts mitochondrial activity in cancer cells, leading to DNA damage and activating pathways that inhibit cancer progression. This dual mechanism enhances the cancer cells' vulnerability to 5-FU, resulting in a more effective treatment regimen when both compounds are used together.
In addition to studying the natural compound, the researchers collaborated with medicinal chemists to create a synthetic version of 2-MiCit that showed even greater potency against cancer cells. This indicates the potential for developing new cancer therapies based on microbial metabolites. The research emphasizes the importance of considering the microbiome in personalized medicine approaches.
Funding for the study was provided by organizations including the Leverhulme Trust, the Wellcome Trust/Royal Society, the DFG German Research Foundation, and the Medical Research Council.