A team of researchers at the Bellvitge Biomedical Research Institute (IDIBELL) has made an important advance in the study of Ewing’s sarcoma, the second most common bone tumour among children and adolescents. The research, published in the journal Molecular Oncology, has been led by Dr. Mariona Chicón-Bosch and Dr. Óscar M. Tirado, and uses multi-omics techniques to decipher the mechanisms that drive metastasis, the main cause of low survival in this type of cancer.
This tumour, diagnosed mainly in patients between 10 and 20 years of age, is relatively rare but highly aggressive. Its ability to spread to other organs considerably limits treatment options, especially in advanced stages.
An animal model and a multi-omics approach
The study is based on an animal model developed by the IDIBELL team, which allows to analyse the development of metastasis. This model involves the implantation of tumour cells derived from human patients in immunodeficient mice, accurately recreating the biological processes involved in metastatic spread.
Using multi-omics tools, the researchers integrated transcriptomic, proteomic and epigenetic data to identify key signalling pathways in tumour progression. Transcriptomic analysis has revealed genes activated during progression, while proteomics has highlighted proteins essential in processes such as cell migration. In addition, the use of DNA methylation techniques has provided information on epigenetic changes that regulate the expression of these genes.
This approach allows a global and integrative view, which is key to understanding the mechanisms underlying Ewing sarcoma.
Key discoveries: CREB1 protein and LOXHD1 gene
Researchers have identified the prominent role of the CREB1 protein and the LOXHD1 gene in cell migration and tumour clone formation. CREB1 acts as a central regulator that modulates the expression of genes associated with tumour invasion. Among these genes, FGD4, a CREB1 target, stands out connecting different biological layers analysed. This gene could be key in the structure and motility of tumour cells, making it a promising target for new therapies.
Implications for the future
According to Dr Chicón-Bosch, ‘the multi-omics approach has allowed us to explore Ewing sarcoma from an integrative perspective, identifying crucial mechanisms to slow disease progression’. Dr Tirado adds that these results could facilitate the development of drugs targeting the identified molecular pathways, offering more personalised and effective treatments for patients. In addition, these findings could have applications in other types of cancer with similar characteristics, broadening the impact of this research.
This project has been possible thanks to the collaboration between different national and international institutions, including the Pediatric Cancer Center of Barcelona, the University of Santiago de Compostela and the German Cancer Research Center (DKFZ). The combined resources and expertise of these institutions has been fundamental to carry out a comprehensive study.
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).