Enrique de Álava: Uncovering a Molecular Vulnerability in Ewing Sarcoma

Enrique de Álava, Professor of Pathology at University of Seville, shared  post on LinkedIn:

“Uncovering a molecular vulnerability in Ewing sarcoma
Our New publication in Oncogene 

I’m very pleased to share our latest article, just published in Oncogene, where we describe a novel mechanism that helps explain why Ewing sarcoma —a rare but aggressive pediatric tumor— is particularly sensitive to irinotecan, a topoisomerase I inhibitor commonly used in relapsed disease.
This work is the result of a fruitful collaboration between my group and that of Dr. Fernando Gómez-Herreros, both at the IBiS Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Hospital Universitario Virgen del Rocío, and it reflects the outstanding work of Dr. Joaquín Olmedo Pelayo, whose PhD thesis we have co-supervised.

In brief:
The fusion oncogene EWS::FLI1, which drives Ewing sarcoma, interacts with the helicase DHX9, impairing the resolution of R-loops — hybrid DNA/RNA structures that cause genomic instability and replication stress when not properly managed. This creates a vulnerability that irinotecan can exploit.
Importantly, high DHX9 levels are associated with poor prognosis, and disrupting the EWS::FLI1–DHX9 interaction or combining irinotecan with ATR inhibitors may provide new therapeutic options.

As Fernando puts it:
“We’ve uncovered a specific vulnerability in Ewing sarcoma that opens up new therapeutic possibilities.”

From a clinical perspective, I believe this work contributes to understanding how to stratify patients better and design more rational and personalized treatment strategies for this challenging tumor.

This has been a genuinely collaborative effort, with contributions from outstanding institutions including: CIBERONC, Instituto de Salud Carlos III, Barcelona Children’s Hospital Sant Joan de Déu, Fundación Instituto Valenciano de Oncología (IVO), University of Valencia, DKFZ German Cancer Research Center, Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg University, IRCCS Istituto Ortopedico Rizzoli.”

Centro de Estudios Biosanitarios (CEB) shared a post by Enrique de Álava, adding:

“Congratulations to Prof. Enrique de Álava!

We are proud to celebrate the latest achievement of Prof. Enrique de Álava, faculty member of our Master in Molecular Oncology, whose new paper has just been published in Oncogene.

This outstanding work, carried out in collaboration with Dr. Fernando Gómez-Herreros and colleagues at the IBiS Instituto de Biomedicina de Sevilla, reveals a novel molecular vulnerability in Ewing sarcoma, a rare but aggressive pediatric tumor.

We congratulate Prof. de Álava and his team for their remarkable contribution to advancing cancerresearch and improving treatment perspectives for pediatric patients.

At the Centro de Estudios Biosanitarios (CEB), we are proud to have leading experts like Prof. de Álava sharing their knowledge and experience with our students.

Interested in joining our global network of oncology professionals?

Our Master’s Program in Molecular Oncology features an elite faculty from prestigious institutions such as the IBiS Instituto de Biomedicina de Sevilla, CNIO – Spanish National Cancer Research Centre, UCL, Beth Israel Deaconess Medical Center and more.
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Title: EWS::FLI1-DHX9 interaction promotes Ewing sarcoma sensitivity to DNA topoisomerase 1 poisons by altering R-loop metabolism

Authors: Joaquin Olmedo-Pelayo, Esperanza Granado-Calle, Daniel Delgado-Bellido, Laura Lobo-Selma, Carmen Jordan-Perez, Ana T. Monteiro-Amaral, Anna C. Ehlers, Shunya Ohmura, Daniel J. Garcia-Dominguez, Carlos Mackintosh, Angel M. Carcaboso, Javier Alonso, Isidro Machado, Antonio Llombart-Bosch, Katia Scotlandi, Thomas G. P. Grünewald, Fernando Gomez-Herreros, Enrique de Alava

Read the Full Article.

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