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Nicola D’Amelio (right), Fundación Occident Visiting Professor, with Jorge Martínez Torrecuadrada, head of the CNIO Protein Production Unit. /MadMoviex. CNIO

Chemist Nicola D’Amelio is developing a new idea at the Spanish National Cancer Research Centre (CNIO) to prevent cancer from becoming resistant to treatment.

His dream is to create probiotics (such as the bacteria found in yogurt) that release a protein capable of slowing the growth of a cancer in the colon, for example. “We are still a long way from that, but the results are promising,” he says.

The Fundación Occident Visiting Researchers Program has made it possible for D’Amelio, a researcher at the University of Picardie Jules Verne (France), to spend time at the CNIO.

Researcher Nicola D’Amelio, from the University of Picardie Jules Verne (France), has spent part of the summer at the Spanish National Cancer Research Centre (CNIO) developing an idea that could, in the future, turn a scene that is currently science fiction into reality: a cancer therapy that you eat… like yogurt.

It is an innovative strategy aimed at preventing the development of treatment resistance; in other words, it tackles one of the main problems in modern oncology: a therapy that was working well suddenly stops being effective, and the cancer progresses.

D’Amelio is developing his strategy together with Jorge Martínez Torrecuadrada, head of the CNIO Protein Production Unit, thanks to the Fundación Occident Visiting Researchers Program.

The key: ‘interfering peptides’ that disrupt cellular communication

The idea is based on small proteins called interfering peptides, which are custom-designed in the laboratory to disrupt chemical signals that are essential for cancer cells.

Tumor cells depend on a physical chain of transmission in order to grow: protein A must fit perfectly with protein B in order to pass on the signal to multiply. Interfering peptides act like a counterfeit puzzle piece. They bind to protein A and physically block the site where protein B should fit. By interrupting this contact, the chain of messages is broken and the tumor stops growing.

Many cancers mutate in order to evade drugs; this means that their proteins change. This is where D’Amelio’s idea comes into play: if, in order to reject the interfering peptide, the cancer changes the shape of its proteins, it also loses the ability to connect with its own proteins, and the chain of messages is interrupted.

“That is why these peptides are such a promising tool,” explains D’Amelio.

Why make them ourselves when bacteria can do it better?

But it is never easy to turn an idea into reality. Creating the right interfering peptides is a challenge. One major obstacle is the relatively high cost of manufacturing them in the laboratory.

D’Amelio has a solution: “Delegate their production to bacteria that we already use safely as probiotics.” Today, it is possible to genetically modify these beneficial bacteria (such as those found in yogurt) so that they act as “microscopic factories.”

“This way, the bacteria not only produce the interfering peptides naturally and much more cheaply, but also release them directly into the intestine,” the researcher explains.

The future: a yogurt that treats colon cancer

This is the dream: to eat probiotics, such as the bacteria found in yogurt, that release a peptide capable of disrupting proliferation signals from a cancer in the colon, for example.

The development of these probiotics is being carried out in collaboration with the CNIO and also with Luis Bermúdez-Humarán of the Micalis Institute in Jouy-en-Josas (Paris).

“We are still a long way from that,” says D’Amelio. “But the experiments we have carried out over these past few weeks at the CNIO have produced some promising initial results.”

A chemist by training, D’Amelio has tested the functionality of several peptides he designed himself in different cell lines at the CNIO.

A “fundamental” stay at the CNIO

“The stay at the CNIO has been fundamental in helping us clarify part of the mechanism of action of the interfering peptides,” he says. “We have confirmed that they can penetrate cancer cells, thereby reaching the target proteins responsible for cell proliferation.”

The next step will be to test the peptides’ activity against a wide variety of cancer cells. It will also be necessary to ensure that they do not degrade before reaching their target.

“Once these preclinical in vitro tests have been successfully completed, we will be in a position to move on to in vivo studies,” says D’Amelio.

“The CNIO offers an enormous number of opportunities for collaboration, thanks to its large number of laboratories, its conference program, and the great availability of its staff. On many occasions, I have been able to obtain reagents, materials, or equipment kindly provided by neighboring laboratories with which I had no previous contact. In addition, the interaction with Jorge Martínez Torrecuadrada has been fundamental. His expertise in cloning techniques is essential for successfully genetically modifying the bacteria that will produce the peptides.”

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