From virtual biopsy to fluorescence-guided surgery: we approach the research of the Molecular Oncology Group of the IIS Aragón

We take a tour with researcher Alberto Jiménez Schuhmacher of some of the research carried out in the Molecular Oncology group at IIS Aragón, which he has led since 2017, and he tells us about the satisfactions and difficulties involved in dedicating himself to science.

Alberto Jiménez Schuhmacher is one of the best-known Aragonese researchers in the media, and he is so for his extensive career in cancer research and also for his extensive experience as a scientific communicator, a task that he considers fundamental to achieving a more cultured and better society. informed.

Since 2017, Schuhmacher has led the Molecular Oncology group at the Health Research Institute (IIS Aragón), whose laboratory is located at the Aragon Biomedical Research Center (CIBA) and has been an ARAID researcher since 2020. The group combines a wide range of molecular biology techniques, experimental models, screenings and cell biology assays in its research. with the aim of developing new diagnostic tools and new treatments against cancer.

Its Current lines of research are: 'Virtual Biopsy: Development of new non-invasive immunodirected imaging techniques for the diagnosis and monitoring of tumors'; Biomarker Guided Surgery: Development of immunotargeted tools against biomarkers to support fluorescence-guided surgery'; 'Development of new immunotherapies and theragnostic treatments against cancer' and 'Identification of modulating genes and therapeutic targets in RASopathies'.

Together they work developing tools for imaging diagnosis. Conceptually, they develop “contrasts” that attach to a tumor when it has certain characteristics. These contrasts are actually nanoantibodies that attach to biomarkers. In addition to being able to see them by image, since nanoantibodies go to the tumor and stick, they are looking for new applications that facilitate surgery, diagnosis or treatment. In addition, the group maintains a social commitment with a line of research focused on rare diseases, known as RASopathies, seeking new diagnostic methods and treatments.

The number of researchers in this group “is fluctuating” and, although it is now made up of six people, Schuhmacher anticipates that the idea is to have two more researchers, to “have a group that does not exceed eight people so that it can be more manageable.” ”. He also points out that “we must keep in mind that for many things we have support from specialists who have scientific-technical services, so, although there are six of us in the group with a view to being eight, it turns out that in the end among those of us who collaborate or participate More than 50 people got together,” he adds.

A virtual biopsy?

One of the group's main lines of research is called 'Virtual Biopsy: Development of new non-invasive immunodirected imaging techniques for the diagnosis and monitoring of tumors'. Almost all of us have heard of biopsies (those processes consisting of the removal of a fragment of tissue from some part of the body in order to examine it to check whether or not there is the presence of a disease), but what is a biopsy? virtual biopsy? Schuhmacher explains it like this: “We all understand that an x-ray is an X-ray photograph that tells us if a bone is broken or that an ultrasound is a sound photo that tells us, if a woman is pregnant, how the baby is doing. Well, there is a very sensitive technique, positron emission tomography, which also gives us a lot of information, and tells us about biology, although currently there are few things that we can look at with a positron emission tomography scanner, the famous PET.”

What is mainly looked at with this tomography is the sugar (which emits positrons), which accumulates in cells, for example, tumor cells. “What if we could have part of the information from a biopsy through a PET image with contrasts that stick to the tumor when it has a certain characteristic? This would tell us about the biology of the tumor, not only its anatomy. What we have developed in the laboratory are contrast agents that stick to the tumor only when they have certain characteristics and we can see them with a scanner. We have called it 'virtual biopsy' because we can see that we have part of the information from a biopsy, but from the entire tumor," adds the researcher.

Jiménez Schuhmacher explains that "this biopsy, today, will not be able to replace the usual biopsies because they are needed to diagnose, but they can serve to complement and perhaps in the future, in some cases, it can even become a substitute."

They began working on this technique called virtual biopsy in the Molecular Oncology group from its beginnings, but it had a great boost as a result of a project that began at the end of 2018 funded by Aspanoa (the association that cares for children in Aragon with cancer and their families) and which consisted of improving the diagnosis of diffuse trunk glioma, a type of brain tumor almost always pediatric that has an average life expectancy of only 9 months and in which the survival rate five years after diagnosis is of only 1%.

Because of the area in which these tumors grow – in the brain stem – “trying to pick up a small piece of tumor to analyze it is like a time bomb,” as Schuhmacher describes, and it is precisely in this type of complex tumors to biopsy where “a virtual biopsy makes more sense to support the diagnosis.”

“Today, with all the knowledge there is, we know that many diffuse trunk glioma tumors are not a single disease but rather several and with these techniques we can classify them to test certain therapies,” says Schuhmacher.

A seed that germinates
One project opens the doors to many more. To develop “contrasts” to study this childhood tumor, the Molecular Oncology group has generated several collections of nanoantibodies, “which is known as a library and contains hundreds or even millions of nanoantibodies that are the basis of these contrasts” that now “we have collections that help us fish for nanoantibodies against specific targets to do many other things,” explains Schuhmacher.

Once they validate these contrasts, they already have a nanoantibody that sticks to the tumor, so they take the opportunity to investigate other aspects. For example: “We glue fluorescence on them so that they can be used for fluorescence-guided surgery.”

“Some of these contrast agents have inhibitory functions on some proteins and we use them as if they were drugs. Others we want to study so that they deliver nanoparticles to the tumor. These nanoparticles can be excited with magnetism or with light of a certain wavelength so that they generate hyperthermia, a lot of heat concentrated in one point and kill, 'burn', the tumor in specific areas that you illuminate or that you 'rub' the magnet.' , Schuhmacher lists.

The principal investigator of the Molecular Oncology group points out that “these contrasts can serve to modify defense cells so that they go to the tumor and recognize it when they have the target protein,” with what we know as advanced therapies, such as the famous CAR-cells. T. As a summary, it should be noted that “we have like a seed that is germinating. We try to nourish the plant so that it produces flowers and good fruits.”

Science, that drug that hooks
Research is synonymous with investing many hours, knowledge and effort in a project that may end up being fruitless, but when a breakthrough or discovery is achieved, the rush is great. Schuhmacher remembers the words of the Spanish scientist Severo Ochoa who stated: “How bitter are the roots of science but how sweet are its fruits.” Schuhmacher adds that it was also Ochoa who stated that “there was no sensation that a human being could experience that was comparable to what he called “the emotion of discovery.”

“I have been very lucky, I have been able to experience that emotion of discovery and it is an indescribable feeling. Some of us say that it is like a drug and it gets you hooked,” says the scientist. He cites as an example the occasion when he was “the first person in human history who could see the expression of a gene he was studying in the cerebellum. You think about it and say “wow, I'm the only person in the world who knows this.”

“In addition, if you have interaction with many patients, as I do, from associations or cancer patients and you see the hopes they have placed in you, it is an enormous responsibility, a great pressure but also an unmatched satisfaction to think that your work is highly valued. for the people,” emphasizes the researcher.

the other side of the coin
However, dedicating yourself to science is not easy for multiple reasons, among them because “science is not well organized, there is no good structure, the scientific career is not completely clear, it does not mean that because you do things well and If you work properly you can have a more or less guaranteed reintegration into the science system,” explains Jiménez Schuhmacher.

The scientist also denounces as part of the problem that “funding is not adequate” and that “there are not enough places to absorb doctoral or postdoctoral students” and, therefore, “it is difficult to retain talent.” He also points to the existence of a “suffocating bureaucracy and expense control that leads us to justify everything many times.” He adds that, to all this, we must add that they have money allocated for research but, currently, inflation makes materials worth “20% or 30% more and there are materials that have doubled or tripled in price during the pandemic for needed for PCRs, vaccines, etc.”

The researcher believes that to improve the quality of research, “sustained funding is needed, maintained over time, with clear and defined calls over time.” Although he celebrates that this year there will be more investment, he emphasizes that it will be positive as long as this investment is “sustained over time” because “what does not make sense is that I grow my laboratory to 12 people and then it is unviable.” maintain them when you have already dedicated many resources to training them.” And he remembers: “A research team takes many years to assemble but you can destroy it in a year. Retaining talent is very difficult.”

Do you remember when science saved us from Covid-19?
Surely, one of the most complex situations that we have experienced as a society in recent decades has been the pandemic caused by Covid-19 and Schuhmacher believes that “we are totally forgetting that science has saved us.” “I think that we have not learned yet, and that Covid has given us very strong, that science is an investment, not an expense, and that in the pandemic it has saved us having knowledge of modified RNA to make vaccines, nanoparticles to to be able to encapsulate it etc.”, he emphasizes.

Betting on research pays off (and we are seeing it)
Regarding cancer, Jiménez Schuhmacher assures that “we have to bet on certain areas of research in the country and be aware that we are living in a moment of revolution in cancer. Either we investigate now, we generate patents, we license and we are the ones who receive the money for doing it or in a few years we will pay other countries for medicines. This is so. Furthermore, in the place where research is carried out, patients benefit first.”

Despite all the difficulties mentioned, Schuhmacher encourages that “as a country we believe in it more” because “we have very well-trained people, good centers and researchers.”

“Lately I have been talking to many researchers and science managers and they tell me, but what is happening in Aragon that resonates more and more? This is clearly because there are institutions that are doing it very well,” she states. Among them he mentions ARAID, “which is recruiting talent, it is a talent magnet” and also “the IIS Aragón, where I work, which has been reaccredited by the Carlos III Health Institute and that gives a seal of guarantee, of getting things done.” very good". Schuhmacher highlights that there are very powerful research groups at the University and Aragonese research centers, where “there is a very good symbiosis between the bio and engineering parts that is bearing very good results. It is exciting that Aragon is talked about, it is very proud.”

Dissemination: the necessary step to reach society
Schuhmacher writes opinion articles in Heraldo de Aragón, has written, together with the writer Begoña Oro, the book 'You so cancer and I so virgo' and recognizes himself as “a believer in scientific dissemination.” He has opted for it “even when before you were penalized for doing scientific dissemination because it was thought that you were not a good scientist if you did it, when for me it is the opposite.” He maintains that “in order to tell science to another person I have to understand it very well and for that you have had to study more.”

How does scientific dissemination influence society as a whole? “I think it is important to educate society so that it understands the revolution we are entering,” says Schuhmacher, pointing out, for example, “how new neurotechnologies are going to change our lives.”

“I believe that by disseminating information we return to society the economic effort it makes with its taxes and we justify what we are doing. Also being able to explain what we do helps to have an educated society that can make better decisions and avoid things like what we saw when the Covid-19 vaccines came out where people said there were microchips and things like that,” declares Schuhmacher.

“In the end, scientific news is good news and I think it is important to tell the progress and tell it well, with a lot of reflection and I believe that society is capable of understanding it. If people see what we do and understand it, how can they not support it?” reflects the researcher.

Source: goaragon, Laura Latorre

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