Targeting R-loop Stability in Ewing Sarcoma - Stand Up To Cancer

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SU2C-CRUK Pediatric Cancer New Discoveries Challenge:
Targeting R-loop Stability in Ewing Sarcoma

Grant Term: January 2021-September 2023

The SU2C-CRUK Pediatric Cancer New Discoveries Challenge is a new, focused effort to spark novel approaches and new collaborations from investigators both within and outside the field of pediatric cancer research, with the ultimate aim of increasing the number of innovative and effective approaches to treating pediatric cancers. This program will support collaborative, multi-disciplinary, multi-institutional, trans-Atlantic Teams to pursue a transformative change in our understanding of the drivers of pediatric cancers and the development of novel or repurposed medicines, treatment strategies or technologies. With a clear and rational line of sight to the clinic, these projects will have the potential to significantly impact pediatric cancer patients, including teenagers and young adults.

Supported by:


Ewing sarcoma (EwS) is a poorly understood pediatric cancer, even with the knowledge of the genetic alteration, EWSR1-FLI1, that drives these cancers. Treatment has not made much advancement, and standard of care consists of surgery, radiation, and chemotherapy. These treatments can have long-term effects, and should they fail, there is no established second line treatment. The Team recently discovered that this gene alteration caused a strong increase in the formation of R loops, which are RNA:DNA structures where RNA is threaded into the DNA instead of being used as a protein template. The Team has proposed to investigate this unique biological hallmark of EwS and if it could be a novel therapeutic target. They also propose the long-term goal of either using available compounds or developing novel compounds towards this unique target.

Pediatric New Therapies Challenge Overview


This is a collaborative, multi-disciplinary, multi-institutional, trans-Atlantic Teams Research Team that includes expertise beyond pediatric oncology (e.g. other areas of oncology, biology, chemistry, engineering, physics, etc.) and investigating one or more of the following concepts: the basis of tumor initiation and progression; novel therapeutic approaches; development of novel biomarkers or methodologies to predict disease progression, to enhance efforts in primary and secondary prevention and intervention; novel models that would enhance pre-clinical research; development of more effective and/or less toxic treatments to improve long-term health and quality of life.


Alexander Bishop, DPhil
UT Health San Antonio

Kevin Hiom, PhD
University of Dundee

Chun Wei-Chen, PhD
Beckman Research Institute of the City of Hope
Principal Investigator

Sneha Prabhu, MPH
UT Health San Antonio
Project Manager

Laura Jean Rutledge
Rutledge Cancer Foundation

Gregory Aune
UT Health San Antonio


Links to publications will be posted when they are available.


Cancer clinical trials allow researchers to study innovative and potentially life-saving new treatments. The goal is to find treatments that are better than what’s currently available; in fact, the therapies offered to today’s cancer patients were almost all studied and made possible by people participating in clinical trials. But many cancer clinical trials aren’t completed because not enough people take part.

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