Scientists “improve the mother” to create a powerful molecule of cancer killers

A bacterial molecule improves chemotherapy. Its synthetic shape could inspire new cancer drugs.

An international group of researchers, led by teams from the MRC of Medical Sciences (LMS), Imperial College LondonAnd the University of Cologne has discovered that bacteria living in tumors can generate a molecule that influences the development of cancer and improves the effectiveness of chemotherapy.

Although microbes are generally recognized for their roles on the skin or in the intestine, more recent results show that tumors also house their own bacterial communities. Scientists are now working to understand how these microbes associated with tumors shape cancer growth and body response to treatment.

In a study published online in Cellular systemsThe researchers reported a major breakthrough: they identified a strong anticancer compound made by bacteria linked to colorectal cancer. This discovery opens up new therapy possibilities, including drugs designed to amplify the advantages of existing treatments.

Discovery of a bacterial metabolite

To reach this observation, the team carried out an extended screening process, testing more than 1,100 conditions in the microscopic green C. Elegans. They discovered that E. coli he produced a molecule known as 2-methylisocitrate (2-microcie), which could increase the power of the 5-fluorouracil (5-FU) chemotherapy medication.

Computer modeling has shown that the microbiome associated with the tumor (bacteria located in and around tumors) in patients also had the capacity to produce 2-12. To validate these results, scientists have tested the molecule in two additional systems: cultivated human cancer cells and a model of colorectal cancer. In both cases, 2-12 demonstrated a strong anti-cancer activity and in the fly model, it was able to extend the lifespan.

Professor Filipe Cabreiro, leader of the co-metabolism group of the microbe host at LMS, and group leader of the Clacad Research Cluster in Cologne, explains the meaning of the discovery: “We know that bacteria are associated with tumors, and now we are starting to understand the chemical conversation they have with cancer cells. We found that one of these chemical strands can act as a powerful partner for chemotherapy. Cancer cells and make them more vulnerable to medication. »»

How 2-12 disrupts cancer cells

The study revealed that 2-12 operates by inhibiting a key enzyme in mitochondria (structures within cells that generate energy for cellular functions) of cancer cells. This leads to DNA Damage and activate the known ways to reduce the progression of cancer. This several-component attack weakens cancer cells and works in synergy with 5-fu. The combination was significantly more effective in killing cancer cells than in one or the other compound alone.

Dr. Daniel Martinez-Martinez, a postdoctoral researcher at the LMS and the first author of the article, says: “Microbes are an essential part of us. That one molecule can exert such a deep impact on the progression of cancer is really remarkable, and another proof on the way in which we can only scrape the surface of what really happens. “

In collaboration with medicinal chemists, researchers have also changed the compound in 2 micro to improve its efficiency. This synthetic version has proven to be even more powerful to kill cancer cells, demonstrating the potential to develop new drugs based on natural microbial products. Filipe adds: “Using the natural microbial product as a starting point, we were able to design a more powerful molecule, effectively improving mother nature.”

These exciting discoveries underline how the microbiome associated with cancer can have an impact on tumor progression and how metabolites produced by these bacteria could be exploited to improve cancer treatments. These results are also important in the context of personalized medicine, stressing the importance of considering not only the patient, but also their microbes.

Reference: “Modulation of chemotherapy by a microbita metabolite associated with cancer” by Daniel Martinez-Martinez, Tanara c. Peres, Leonor Quintaneiro, Cecilia Catra, Maksym Cherevatenko, Stephen J. Cutty, Lena Best, Despoina Chrysossoms, Despoof Joao B. Mokochinski, Alex Montoya, Susanne Brodeer, Michalina Zatorska, Timothy Scott, Ivan Andrew, Holger Kramer, Masuma Begum, Bianarard T. Golding, Julian R. MalCi, Susumu Hirabayashi, Christophy yesterday, Alexis R. Bar, Christian Cachemé, September 10, 2025, Cellular systems.
DOI: 10.1016/J.CELS.2025.101397

This study was mainly funded by the Leverhulme Trust, the Wellcoma Trust / Royal Society, the DFG German Research Foundation and the Medical Research Council.

Never miss a breakthrough: join the Scitechdaily newsletter.