This Week in Pediatric Oncology #107 - February 9, 2023

Our host, Dr. Timothy Cripe from Nationwide Children's Hospital, is joined by Dr. Martin McCabe from the University of Manchester to discuss the results of the rEECur trial. The rEECur trial is an international randomized trial conducted on recurrent and primary refractory Ewing sarcoma patients. Dr. McCabe leads a discussion on the genesis of rEECur, what it entailed & what was learned from conducting this trial.

To learn more about this trial, please visit https://www.manchester.ac.uk/d....iscover/news/study-i

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Lucas turned 18 in the hospital, but still found himself in the children's wing as he went through his chemotherapy treatments. He wasn't able to attend his senior year of high school. But even when he was at his lowest points, Lucas never gave up hope.

"[Cancer] has changed me completely and it's made me the person I am; I like to think that's a better person. It's definitely a lesson in life, and if you listen to it it will teach you a lot." - Lucas

#50states50stories #TeenCancerAmerica #tyacancer

One young person is diagnosed with cancer every hour. To see what you can do go to: https://www.teencanceramerica.org/donate/

Genes & Cancer published this research on December 27, 2021 as the cover for Volume 12, 2021, entitled, "EZH2 suppresses endogenous retroviruses and an interferon response in cancers" by researchers from the Greehey Children’s Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX; Mays Cancer Center, The University of Texas Health Science Center, San Antonio, TX; Department of Biochemistry and Structural Biology, The University of Texas Health Science Center, San Antonio, TX.

DOI - https://doi.org/10.18632/genesandcancer.218

Correspondence to - Yuzuru Shiio - shiio@uthscsa.edu

Abstract

Ewing sarcoma is an aggressive cancer of bone and soft tissue in children. It is characterized by the chromosomal translocation between EWS and an Ets family transcription factor, most commonly FLI1. We recently reported that Ewing sarcoma depends on the autocrine signaling mediated by a cytokine, NELL2. NELL2 signaling stimulates the transcriptional output of EWS-FLI1 through the BAF chromatin remodeling complexes. While studying the impact of NELL2 silencing on Ewing sarcoma, we found that suppression of NELL2 signaling induces the expression of endogenous retroviruses (ERVs) and LINE-1 retrotransposons, an interferon response, and growth arrest. We determined that a histone methyltransferase, EZH2, is the critical downstream target of NELL2 signaling in suppressing ERVs, LINE-1, an interferon response, and growth arrest. We show that EZH2 inhibitors induce ERVs, LINE-1, and an interferon response in a variety of cancer types. These results uncover the role for NELL2–EZH2 signaling in suppressing endogenous virus-like agents and an antiviral response, and suggest the potential utility of EZH2 inhibitors in enhancing anti-tumor immunity.

Keywords - endogenous retroviruses, Ewing sarcoma, EZH2, interferon response, NELL2

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Army veteran Brandi Benson was diagnosed with stage 1B soft tissue Ewing sarcoma at 24 years old. Hear about her diagnosis, chemotherapy, surgery, and recovery.

For the full story, check out: https://www.thepatientstory.co....m/cancers/sarcoma/so