Arkaitz Carracedo, researcher: “If cancer were not a disease, this would be a better system for studying evolution” | Trends | Project

Arcatis Carracedo (Bilbao, 44 ​​years old) has not stopped asking himself questions since he decided to devote himself to cancer research. He studied health biology in Madrid, where a professor encouraged him to follow a path of research and, in particular, try to understand why tumor cells act the way they do. These and other questions led him first to Memorial Sloan-Kettering Cancer Center Hospital in New York and then to leading his own team at the CIC BioGune Institute, a biotechnology center located in the Vizcaya Technology Park in the Basque Country. . The group focuses its research on cancer metabolism, how cancer cells act, what pathways they follow within the body, and how to identify them to develop treatments.

This research allowed him to win the National Youth Research Award in Biology in 2022, the Astra Zeneca Young Investigator Award in the Oncology category last year, a starting grant and then a consolidation grant from the European Research Council (ERC) or Ramiro Carregal. 2024 Emerging Talents in Cancer Research Award and other awards. Carracedo spoke with EL PAÍS via video link and said that researchers must be creative and open to answering the same question from different perspectives. “This leads to truly innovative research.”

Question: What is cancer metabolism?

A: A normal body cell, already developed, performs a function similar to a factory worker. The liver is responsible for detoxification, skin cells protect us, and intestinal cells filter food. When cells, due to errors they make in dividing or due to external agents that can increase the rate of errors and mutations, transform into cancer cells, they also change their purpose. It begins to divide, grow and survive.

Question: And what does it mean?

A: Let’s think about how we eat at different stages of our lives. For example, a 30-year-old woman might eat based on whether she exercises or not, as well as how much she moves and how much physical activity she has, to be balanced. However, a pregnant woman probably eats the same thing, maybe a little more in quantity, but her body directs the food to completely different functions that generate biomass, a new organism. Cancer cells also change their program. They use food to produce biomass, lipids, membranes, genetic material, and proteins, among other things. All this requires changes in the way food is metabolized.

Metabolites, which are small molecules (that arise from metabolic pathways), serve many other purposes. For example, to remodel the tumor microenvironment. It’s like we use the concrete we have at home to pave the streets. They go beyond what they need to grow and use it to change their environment to help them survive better.

Question: Could understanding how tumor metabolism works hold the key to developing treatments?

A: We can see this in retrospect. 100 years ago, researcher Otto Warburg discovered that cancer cells use much more sugar than normal cells. This is an original observation, and if I tell it, someone will probably say: “Okay, what is this for?” This is what is called basic research, and the criticism is usually that this is knowledge, but what is its application? Thanks to this observation, today the clinic uses an imaging method: they inject specially labeled sugar and see how it is distributed in the body. Cancer cells, because they are much more vulnerable to sugar, glow above normal tissue and we can see where the cancer is. This is very important, for example, for detecting metastatic lesions.

Everything we know about how tumor cells feed can help us detect cancer, and similarly, if we know which roads cancer cells use to transport their goods and what their food contains, we can use drugs to block cancer, and have more effective treatments against it. treatment of the disease.

Question: And prevent it?

A: To prevent this, we will have to take one more step. We think of cancer as growing and developing tools, but as it grows in our body, it is exposed to everything our body is exposed to, and our closest contact with the environment is food. If the diet changes, if we have an unbalanced diet, a very high fat diet, which can lead to obesity, diabetes, etc., all this forces cancer to live in a completely different environment. It has been shown that these lifestyle changes may influence the aggressiveness of the disease.

We need to understand how cancer cells feed, or how they use metabolism more generally, to improve treatment, diagnosis, treatment, prognosis and, moreover, how our lifestyle influences cancer development, aggressiveness and response. treatment to develop preventive policies.

Question: External factors influence the metabolism of cancer, the way it grows inside the body.

A: Not only in cancer metabolism, but in everything that surrounds it. We are well aware of the factors associated with the development of the disease, such as tobacco or alcohol, and they change, for example, how our immune system is able to defend against cancer. The immune system recognizes cancer cells, attacks and destroys them. Thus, people who are immunocompromised, whether due to a drug or a virus such as the HIV virus, are more likely to develop cancer. They are more vulnerable, they have less protection. All the environmental factors that make our immune system more clumsy give cancer an advantage.

Question: Is there progress being made in deciphering how cancer cells work, or are they still largely unknown?

A: We’ve come a long way. If we were talking about Ancient Egypt, we could say that we are getting a good catalog of language and culture, but we still don’t know exactly the details of how all the lineages fit together. We have a catalog of changes that exist in cancer thanks to falling prices and the introduction of cutting-edge technologies such as sequencing. But we don’t know exactly how to predict the disease, how to make an early diagnosis, or how to personalize treatment to ensure that the drugs are most effective for the patient. We are learning this, and every step in this direction is a qualitative leap.

Question: Where are we at?

A: 50 years ago, one in four patients diagnosed with cancer did not live more than five years, and today the five-year survival rate is more than 50%. This step by step has had a huge impact on cancer survival, for example through the development of technologies that allow us to detect traces of cancer in the blood (called liquid biopsy) or train our immune system so that we can find cancer like a bloodhound. All this makes cancer more treatable, but we still have serious problems. There are types of cancer that we know little about, that are diagnosed late or that are difficult to operate on: lung, pancreatic or brain cancer. For one reason or another, we don’t yet have all the tools to make significant progress.

Question: What do you think will be the next big thing in cancer research?

A: There are various areas in which progress is being made in a very significant way. For example, precision therapies, the fact that the most advanced sequencing technologies are increasingly becoming available for adoption by healthcare systems. This will allow us to personalize treatment beyond superficial or specific analysis, and instead of just seeing the cover of a book, we will be able to read all the chapters.

Question: Is it possible to teach the immune system to recognize tumor cells by studying the metabolic pathways of cancer?

A: First, we must stratify better, that is, separate patients better. Then better train your immune system to attack the tumor. And this is done in different ways. Cancer is developing tools to make itself invisible to the immune system. Immunotherapy awakens the immune system to attack the tumor. This is something that is already in the clinic and causes a reaction in a cancer that has not responded to treatment and that has not failed under any treatment regimen. But we still don’t know very well who will respond and who won’t. We know that a third of patients receiving these drugs respond to them.

They also take cells from the patient’s blood and, knowing what characteristics the tumor has, modify these cells so that they are able to identify cancer. It’s like giving them GPS data about where and how the tumor is located and feeding it back into the patient. This is a very personalized approach, but it produces good results. The final step is a liquid biopsy to detect the earliest markers of cancer in the blood so that an early diagnosis can be made.

Question: Do you think now is the right time for cancer research in Spain?

A: It’s a good time because we have a generation of tremendous talent. We have very well trained people, young people who come with innovative ideas and who, despite the poor funding that still exists compared to other countries, manage to create very competitive research areas. The difference will be whether these people can develop their abilities to their full potential.

Question: What is needed for this?

A: Long-term, sustainable strategic investments that focus on creating knowledge and insights that generate innovation. It does not generate innovation directly. We must develop research careers, which are currently too simplified. It’s like if you work for a newspaper and the goal of all your colleagues is to be the editor of the newspaper. We need trained and excellent people in all professional fields. This is not yet sufficiently established in science.

Question: What is the main question you are trying to answer in your research?

A: If I had to group all the questions we ask into one, it would be: How does a cancer cell get the tools from our body to progress throughout the course of the disease? It was as if we thought that each of us was given his own tool, and cancer was able to enter the workshop and use them all. It uses embryonic cell programs, placental cells and immune cells. He hacks the entire system to gain access. One of the most interesting things is that if cancer were not a disease, it would be a better experimental system to study evolution because it is an example of how natural selection works.