Spanish researchers identify the cells responsible for relapses in colon cancer after removing the tumor

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Each year around two million new cases of colon cancer are diagnosed in the world.

In Spain, according

report , this year

.

It is the most common tumor, ahead of breast and lung.

Although most of these diagnoses arrive when the tumor is still localized, removed and then treated with chemotherapy with the intention of avoiding relapses, in

.

The reason for the invasion of other organs is due to

, which are not visible with diagnostic techniques and on which no research had been addressed.

Now,

, ​​led by Dr. Eduard Batlle, ICREA researcher and group leader at CIBER Cancer (Ciberonc), have generated an experimental model in mice and have identified these residual tumor cells for the first time, characterizing how they evolve leading to the appearance of metastases in the liver and lung.

Furthermore, the research, published in the journal

, has shown that

"About five years ago we decided to study this stage of the process about which there is very little information. And, despite being very important at a clinical level, we had very little biological and molecular information; we did not understand which cells were responsible for of this process and how little we could eliminate them," Dr. Batlle tells EL MUNDO.

Colon cancer is made up of different types of tumor cells that exert different functions during the progression of the disease.

Within this cellular amalgam,

which have little proliferative activity and do not contribute to primary tumor growth.

However, "clusters of HRCs are capable of shedding cancer in the colon,

.

In samples from patients with colon cancer, the researchers have been able to confirm the presence of these same cells in patients who have a higher risk of recurrence of the disease after treatment", reports IRB Barcelona.

Batlle explains that at the time of diagnosis and removal of the primary tumor "

, and, therefore, a higher risk of recurrence".

In this sense, he points out that there are already advanced techniques, for example, in blood measurement, with which it is already known "that patients who have tumor DNA, the tumor circulating in the blood after surgery, have a much higher risk of relapse than those who do not.

and more aggressive treatment".

The work of IRB Barcelona researchers has confirmed that eliminating these cells using genetic techniques is sufficient to prevent the formation of metastases;

that is, the mice that develop colon cancer remain free of disease after surgery of the primary tumor, without suffering subsequent relapses.

Therapeutic Strategy

In addition, Batlle's team has developed a therapeutic strategy to eradicate residual disease and prevent recurrence and has also shown that

.

"Relapse in colon cancer is a relatively rapid process compared to other tumors such as breast cancer, in which it occurs much later, between 10 and 20 years. However,

", Batlle points out.

Thus, the study he has led suggests "a review of the clinical guidelines for treating this type of cancer, because, in many cases, it would be advisable to apply immunotherapy before surgery. A treatment that has already been shown to be effective and safe against other tumors and that has been able to eliminate and prevent residual disease in experimental mouse models", concludes Batlle.

Lluís Espinosa, coordinator of the Research Group on Molecular Mechanisms of Cancer and Stem Cells at IMIM-Hospital del Mar, in a statement to the

points out that "the fact that this population of cells with a high probability of relapse may be sensitive to immunotherapy suggests that

."

For Alberto J. Schuhmacher, head of the Molecular Oncology Group at the Aragón Health Research Institute, "this work may represent a before and after in the knowledge of metastatic colon cancer. Cancer is an organized cellular crime.

.

Thanks to innovative technologies that make it possible to study individually within a tumor which genes are turned on or off cell by cell, this team of Spanish scientists has identified genes with a high relapse capacity that are responsible for the appearance of metastases in the liver and the lung when it was thought that the primary tumor was localized and had been completely removed". According to him, "this work alerts us that these cells, which are very scarce, are disseminated in many patients and

", and adds: "This contribution could be a revolution and proposes a revision of the clinical guidelines in the treatment of this type of cancer because, in many cases, applying neoadjuvant immunotherapy (before surgery) or future targeted treatments should be considered. to attack these cells.

Schuhmacher acknowledges that there is still a long way to go and work to understand "what causes these cells with a high capacity for recurrence, once they have traveled to the liver or the lung, to activate to form metastases. It is still necessary to understand how they originate, what determines their number and why their number varies between patients".

Finally, Ignacio Melero, professor of Immunology at the University of Navarra, researcher at CIMA and co-director of the Department of Immunology and Immunotherapy at the University Clinic of Navarra, points out to SMC: "

What we already know from recent publications is that preoperative immunotherapy in the subgroup of patients with colon cancer with damage to DNA repair mechanisms (approximately 15-20% of cases) determines that tumor cells frequently disappear in the surgical specimen".

Melero also points out that "as for the most important limitations, there would be the adverse effects of the combination of

[immune checkpoint inhibitors].

Although it is a very interesting model, it may not accurately reflect the immunology of micrometastases in patients."

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