Epigenetic drugs might be useful in the treatment of a very aggressive infantile muscular tumor


A study led by the research group in sarcomas of the Bellvitge Biomedical Research Institute (IDIBELL) directed by Oscar Martinez-Tirado shows that levels of caveolin-1 in alveolar rhabdomyosracoma are undetectable or very low and that genetic reintroduction and restatement by epigenetic drugs, slows the growth of these tumors. The results have been published in the journal Oncotarget.

Rhabdomyosarcoma is the most common muscle sarcoma in children and adolescents. Despite advances in therapy, patients with the variant called alveolar rhabdomyosarcoma have a lower survival rate of 30% five years after diagnosis.

The Oscar Martinez-Tirado’s team studied the expression level of caveolin-1 protein in different types of sarcoma. “We saw that the only cells that did not express it or express it very little were alveolar rhabdomyosarcoma and it looked like they could present some epigenetic alteration that silence its expression” the researcher explains.

“In collaboration with the Program for Epigenetics and Cancer Biology IDIBELL led by Manel Esteller, we analyzed the methylation patterns and saw that, indeed, the promoter of the gene for caveolin was silenced by hypermethylation, so the protein is not expressed. “So that caveolin-1 acts as a tumor suppressor. When levels are low or nonexistent, normal cell differentiation is blocked and facilitates tumor development.

In the market there are drugs that can modify epigenetic alterations. Researchers tested one of these drugs on cell lines to reactivate the promoter of caveolin-1 and promote its expression again. “The reintroduction of caveolin” explains Martinez-Tirado “causes the tumor cells are more likely to differentiate and, as they cannot return to normal activity dies out, thus slowing tumor growth.”

The drugs have only been tested in cell cultures. Currently, the group of sarcomas works to find out which the molecular mechanisms by which caveolin-1 tumor slows tumor growth to transfer its reintroduction by epigenetic drugs are to the clinic.

In this study collaborated IDIBELL, Hospital San Juan de Dios, the Vall d’Hebron Hospital and the Institute of Predictive and Personalized Medicine of Cancer.

Huertas-Martinez J., S. Rello-Varona, D. Herrero-Martín, E. Barrau, S. García-Moncliis, M. Sainz-heather, Lagares-Tena L. Nunez-Alvarez Y., Mateo-Lozano S ., J. Mora, J. Rome, N. Toran, S. Moran, R. López-German, Gallego S., Esteller M., Peinado MA, García del Muro X and M. Tirado O. Caveolin-1 is down-regulated in alveolar rhabdomyosarcomas and Negatively regulated tumor growth. Oncotarget. Aug 27th 2014 Epub ahead of print.

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