Pharmacological inhibition of a protein reduces metastases in Ewing’s Sarcoma in vivo and in vitro models

  • The G9a enzyme increases the probability of developing metastases in these bone or soft tissue neoplasms. However, treatment with its inhibitor (BIX01294) could improve the control of metastasis in patients.
NO025 - OM Tirado_Oncogene - Imatge

A study with the IDIBELL Sarcoma research group participation and led by the Molecular Pathology of Sarcomas group of the Seville Institute of Biomedicine (IBiS) has described that the G9a protein would be associated with the development of metastases in Ewing’s Sarcoma. Therefore, the overexpression of this protein would indicate an adverse prognosis. G9a is an enzyme that modifies DNA epigenetic signals, those that activate and inactivate gene transcription.

Ewing’s Sarcoma is a malignant round cell tumor, mainly pediatric, which is considered a rare disease in which the neoplastic cells are in the bone or soft tissues. 80% of patients with metastasis-free disease overcome the disease with standard treatment. However, in patients who develop metastases, the percentage is around 20-30%. Therefore, research efforts are focused on finding therapeutic alternatives that prevent the development of metastases or can increase patient survival.

In this preclinical study, the researchers propose an alternative to reduce the development of metastases in these patients using a drug, called BIX01294, which inhibits the activity of the G9a protein. The study has shown a significant decrease in cell proliferation and in several processes involved in metastatic development in vitro (migration, adhesion, invasion, and clonogenic capacity) after treatment with BIX01294. Furthermore, BIX01294 slowed primary tumor growth and reduced metastatic development in 40% of the two mouse models.

This work would support future clinical trials in patients in whom BIX01294 could complement the standard therapy of Ewing’s Sarcoma. Successful for those who do not present metastases, but which needs to be improved in those with adverse prognostic, comment the researchers.

Also participated in this work: The Sant Joan de Déu Hospital, the López-Neyra Institute of Parasitology and Biomedicine, the cancer division of Imperial College London, and the Network Biomedicine Research Center (CIBERONC). The study has been financed thanks to a grant to cooperative groups from the Spanish Association Against Cancer and two projects financed by the Carlos III Health Institute (PI17/0464, PI20/0003), as well as the research project of the Ministry of Health of the Junta de Andalucía (PI-0013-2018).

Text adapted from the Seville Biomedicine Institute (IBiS): link


The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).

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