Vall d'Hebron researchers identify a 'switch' that blocks metastasis in an aggressive childhood cancer

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The

(VHIR) in Barcelona has identified an epigenetic "switch" capable of blocking the process of metastasis of neuroblastoma, a pediatric cancer that causes 15% of deaths in children with cancer.

This study in animal models of the VHIR Childhood Cancer and Haematological Diseases group, which has had the collaboration of

, opens the door to new therapies that paralyze the metastasis process.

Neuroblastoma is a rare but highly aggressive disease, accounting

in pediatric cancer patients.

It mainly affects

and originates in immature nerve cells that are found in various areas of the body, being more frequent in the adrenal glands (above the kidneys), although they can also appear in other areas of the abdomen, in the chest, neck, or near the spine.

Increasing evidence indicates that

play an important role in the development and progression of the tumour, which is responsible for determining the expression of genes.

The genetic material of an organism is conditioned by a series of chemical compounds, the epigenome, which act as if they were "switches", since they

In this study, published in the journal

, researchers from the VHIR Neuronal Tumors Laboratory have identified the key role in the evolution of neuroblastoma of a highly altered epigenetic regulator:

"Until now, the role of this epigenetic regulator in neuroblastoma was very enigmatic, but our results shed light on its functions as a regulator of the epigenome of the cells of these tumors, and have allowed us to discover that it is necessary for the expression of a wide set of of essential genes for the metastasis process", stated the first author of the study and VHIR researcher, Dr.

Thus, this study has identified "something similar to an epigenetic switch" capable of

of proteins that are what allow cells to interact with their environment and invade new organs, he added.

Inactivate metastasis

Specifically, the researchers have observed that the inhibition of two subunits of the BAF complex produces its structural disintegration, which makes it possible to epigenetically inactivate the gene expression program that contributes to

.

The effects of this epigenetic reprogramming were tested in mouse models, resulting in a strong blockade of organ invasion by neuroblastoma cells and the subsequent growth of metastases, which allowed

of neuroblastoma cells.

animals.

"In addition to answering big questions about the role of the BAF complex in neuroblastoma and contributing to our understanding of the epigenome of these tumors, this study represents an important step in the development of new epigenetic therapies for the treatment of a highly metastatic disease and aggressive", highlighted the head of the VHIR Neuronal Tumors laboratory,

.

According to this researcher, the finding is a starting point for "

focused on the generation of an epigenetic therapy for metastatic neuroblastoma with the BAF chromatin remodeling complex as a target".

The study was made possible thanks to funding from the Strategic Health Action of

, as well as aid for hiring predoctoral research staff in training (FI) from the Government of Catalonia and the European Social Fund.

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