The cause of Ewing sarcoma, one of the most aggressive childhood tumors, has been identified.

BarcelonaMost tumors are caused by an accumulation of genetic mutations. Knowing which cells these mutations originate in makes it easier to find treatments that target the cancer more surgically and avoid the extreme side effects of chemotherapy or radiotherapy. However, this is different with pediatric tumors, as the vast majority have very few underlying genetic alterations. This is the case with Ewing sarcoma, a rare type of cancer that occurs in the bones or the soft tissue surrounding the bones. It is cured in 60% of cases, but the toxicity of the treatment causes side effects in the children who receive it.Now, researchers from Hospital del Mar and the San Juan de Dios Research Institute have discovered that this aggressive tumor depends on a single genetic alteration originating in one cell, which they have also identified. "Until now, we thought that the oncogen—the gene that mutates and can produce cancer—needed more genetic alterations to produce the tumor, but now we have seen that this is not the case," explains Dr. Inmaculada Hernández-Muñoz, a researcher in the dermatological inflammatory and neoplastic diseases research group. Hernández-Muñoz details that they have managed to demonstrate that there is only one cell capable of tolerating this dysfunctional protein—the rest die or stop growing—and that a single oncogen is sufficient for the tumor to develop. The discovery, published in the journal Nature Communications, This opens the door to finding less aggressive therapies for Ewing sarcoma, especially considering that it is a tumor that affects children and that its side effects can affect them for life.

"We must keep in mind that Ewing sarcoma is treated with surgery followed by chemotherapy or radiotherapy. The problem is that these therapies target cells that grow, and in the case of children, these are not only the tumor cells," explains Hernández-Muñoz. This is because many normal cells (growth cells, bone cells, nervous system cells, and immune system cells) divide actively in children.

Now, once the cell where the tumor originates is identified, treatment can begin because Treatment in children and adolescents with Ewing sarcoma It is more similar to cancer treatments in adults, for which specific markers have been identified and more tailored therapies have been developed.

Mutation in the embryo

To identify the cell from which Ewing sarcoma originates, researchers have recreated the mechanism that causes the tumor in collaboration with the laboratory led by Dr. Àngel Raya at the Center for Regenerative Medicine in Barcelona. Specifically, they generated and purified embryonic mesenchymal stem cells—those that form the embryonic tissue from which, among other things, the body's muscle and connective tissue, blood vessels, and lymphatic vessels derive—and introduced the oncogen that causes sarcoma-like sarcoma. This model will now allow researchers to study the structure of the cell that gives rise to the tumor and understand what causes it to develop this characteristic. Given that they have verified how the cell of origin of Ewing sarcoma is already present in the fetus during its intrauterine development, Dr. Hernández-Muñoz explains that her hypothesis is that "upon reaching puberty, hormonal factors cause this cell, which already has the gene oncogene, to develop."