“We want to know what happens when normal cells cause cancer,” the researchers concluded Dilena Alonso Cubello. The goal is obviously simple, but at the same time, it is contradictory and ambitious: “Until recently, people did not understand it enough, because technology does not allow it, and it can only be done when it is too late. Research. But understanding what happens in the early stages of cancer is very important to be able to improve diagnosis and treatment.”
The project started six years ago Sloan Kettering Memorial Cancer Center He is from New York, and his thesis arrived after the CNIO in Madrid was completed.The specific purpose is to reveal the beginning of the most common types Pancreatic cancer, Especially Sibilin and lethal. Now, when you plan for your future, Publish results in journals natural.
This is their discovery, this is part of their history.
Cancer attack is big Bang biology. Once a tumor is formed, people know a lot about it, but it started as a small dark moment with many problems. For example, healthy tissues accumulate mutations and DNA changes with age, but in most cases, they are self-limiting and will not develop further. It depends on whether they go further?The current idea is to develop a kind of tumor, a kind of cell Need to receive various Hit, Overcome a series of obstacles. And it seems that many times it doesn’t just happen to accumulate mutations.
In 1985, the research team Mina Bissell Some amazing experiments were proposed. They used a virus that causes chicken tumors and was surprised to find that they only appeared at the injection site.Even if it enters the blood, there is only a virus Acted At the puncture site. In addition, if a puncture is performed on one wing and a wound is simultaneously produced on the other wing, two tumors will appear, one for each tumor. The virus seems to require the environment to break down.
That is one of them obstacle Main The problem that cancer must overcome is the normal microenvironment or the cell’s microenvironment, which is the structure of its protective system.
This is one of the possible explanations why cancer has been cured so many times on a plastic laboratory board. Because there is no environment there.
Direna Alonso (Direna Alonso) in her laboratory. / Picture provided by the researcher.
The most aggressive mutations in pancreatic tumors are very serious. A gene called KRAS. However, this does not seem to be enough to cause cancer, it needs to be more aggressive. Usually, this attack is inflammation of the environment, such as inflammation caused by pancreatitis. Similar to a wound on a chicken wing. “This is something already known, I have shown Alonso explained that Mariano Barbacid (Mariano Barbacid) is in CNIO’s group. I don’t know when the tumor started to occur.
To study it, they used mice with or without mutations that suffered chemical mutations. pancreatitis. Then, they used all the technical means to analyze what happened in the pancreas with or without mutations, and their performance in the face or absence of damage. And, if the cancer starts, then what will happen at the beginning and at the end. Study almost all possible landscapes.
Cells with mutations use the mechanism by which normal tissues can repair and regenerate under attack, but they transfer them to cause tumors
The result achieved the expected effect: in general, neither mutation nor injury caused tumors. These appear when the two situations merge.Alonso explained: “Cells with mutations use the mechanism by which normal tissues can be repaired and regenerated when invaded, but they transfer them to the initial tumor.” “This fits the image of cancer, that is, the wound cannot heal.. Tumors are cells and their condition“.
The biggest challenge is to study what distinguishes tumor cells from normal cells, and what happens so that the pancreas can regenerate without problems in mice without mutations, and mice with mutations start fatal cancers. Alonso said: “We found that there were almost 10,000 changes between one process and another, and we found that some of them not only accompany tumors, but also promote tumor formation.”
The vast majority of these changes are not letters or DNA sequences, but Chemical labeling Associate with it so that it rolls more or less loosely. They are so-called epigenetic changes (above genetics). Generally, they work by turning DNA on or off, allowing or preventing its reading, and are the key to defining a cell’s identity.
DNA opens up in certain areas to provide guidance for cell repair, thereby releasing risks.mutation use The moment the crack appeared and opened the gate, it became uncontrollable. The image is similar to someone spotting a car with a running engine-a KRAS mutation-and trying to steal it, but the doors are closed and the windows closed. You only need to open one of them to remove it.
Only if he succeeds will he see that he has no brakes. Alonso said: “And the GPS is not configured correctly, so it will use it in the wrong way.”
Application and continuation
People who focus on basic sciences often ask a repetitive and certainly annoying question. It is called so not because of its simplicity, but because it does not directly address a specific application. The question is: what is this for?
In the comments attached to the article In Nature, Australian researchers Sane Vassiliadis and Mark A. Dawson concluded: “Because of many of our organizations […] The clones of these cells have mutations that are susceptible to environmental damage. These findings may have profound influence. Their research results should form the basis for future research.
Alonso is well aware of possible profits and some pitfalls. One is that, even if not very simple, it opens the door to the treatment of one of the most deadly and aggressive tumors.In the laboratory, they try to avoid the activation of most genes DivertedTo maintain the brakes of the car (there are some drugs that can do this-BRD4 inhibitors in jargon-although their effects are very common).He explained: “This is effective, but it also impairs the repair of the organ.” “Now we need to make sure specific goals And target tumors that we can successfully attack.”
Another possible application is Early diagnosis, It can be detected before symptoms appear, thereby increasing the options for cure (the main problem with pancreatic cancer is that it is usually detected too late). Alonso said: “If we know what signs are starting to appear, we can look for them in the blood.” This test is called a liquid biopsy and is one of the hopes of fighting cancer, but it has many difficulties. For example, signals that are present in the tumor and only in the tumor can avoid possible misdiagnosis.
Alonso was fully aware of this, so they made an “effort to distinguish it from other diseases such as pancreatitis.” He also realizes that this is not his main goal, and “there are some other experts.” It is clear that “understanding what is happening in the cell is the first step to get there.”
The next question is: what to do now?
Alonso concluded: “The goal is three.” “I want to study which are the most important altered genes in tumors, that is, the specific cells that originated from it, and to better understand the signals from the environment, which will definitely help improve immunotherapy.” All of these, if possible , He wants to do it in Spain. “My dream is to become a scientist without having to give up my country. I don’t want to go back to Spain and retire.”
Alonso with a multi-pipette. /Courtesy photo
Origin and environment: biography
The phrase at the beginning of this article is also the subject of the doctoral dissertation of Direna Alonso, which was conducted at the Madrid CNIO on melanoma or skin cancer.signature Jose Miguel Alonso Fernandez Arcetuno, A recognized Architect and landscape architect from the Canary Islands, He died of melanoma in 2004. He is the father of the researcher.
Like many other biographies, Alonso admitted: “I don’t have a clear career.” “I like many things. I remember thinking in a stupid way. I want to dedicate myself to things that can improve the world. My father then told me. : Any work you do can improve the world, and the most important thing is attitude.
Once he decided to study health-related things, he chose Pharmacy because it integrated many aspects, and in the second year of his career, his father was diagnosed with a tumor.
Alonso said frankly: “This is very difficult.” Alonso was still very excited after thinking about it. “I remember feeling frustrated when I saw that the textbook did not provide a solution to my father’s problem.” At that time she decided to conduct cancer research.As soon as I entered the CNIO talks, the center started a series of Melanoma Research Led by a scientist Marisol Soengas. Alonso joined their team.
Alonso explained: “Since then, several treatments for melanoma have been developed, but there were few at that time.” “Pancreatic cancer today is like melanoma.” In this regard, he thought carry on.
“Fortunately, I have managed Grant from “la Caixa” This helps to go from becoming a post-doctoral researcher to establishing our own research group.” This scholarship can make it easier for him to continue the project, but it is not an easy process to obtain it. He said: “I think we We must begin to pay attention and make failure a natural phenomenon in research more obviously. “
“I did get this scholarship, but others also rejected me. One thing that seemed very positive to me was that in this case, it was approved even before the work was accepted for publication. Although important, our researchers are not only our courses and publications”.
Direna Alonso (Direna Alonso) in Central Park, New York. /Photo provided by researcher.
Now his dream is to return to Spain, although he has not yet made any decision. “The amount of investment in this project in the United States is cruel. He admits that elsewhere, it must be the only project in the entire laboratory, not just another line. “But in Spain, there are some leading groups with very little The funds have carried out very important work. I hope there are more, but we must get rid of the complicated situation unless we attach great importance to it.”
Compared with the United States, Spain has some leading groups that have carried out very important work with very little funds.I hope there are more, but we must get rid of the complicated situation unless we are highly valued
At the end of the conversation, almost someone asked him why he chose New York after Madrid.He replied: “I have been doing papers for a few months.” “This is a city where many things happen in science and culture. The laboratory I came to is very large, it covers many topics, and left behind. A lot of freedom. But he is also known for his entertainment. Moreover, the environment not only affects cells, but also our people. “