Thanks Anton! Important question - my view is that fusion-induced replication stress, like PGBD5 expression, likely contribute to the ATR inhibitor responsiveness of ES (mentioned in Discussion), but whether/how RS impairs the physiologic DNA repair response is less clear to me. Curious your view?

Interested in pediatric cancer and DNA repair? We are recruiting PhD students and postdocs, so please reach out and come join us in NYC. #MSKKids

We would love to hear feedback, opportunities for new directions and collaborations. This is the work of many at UCSF and MSKCancerCenter, but led by 2 super star postdocs
Shruti Menon and Daniel Gracilla.

3. Cell-line and PDX testing of the ATR inhibitor elimusertib as a synthetic lethal therapeutic strategy to target ATM defects across the class of FET rearranged tumors.

2. New mechanistic studies of the interaction/competition between EWSR1-FLI1 (the Ewing fusion) and native FET proteins (i.e., EWSR1) at DNA double-strand breaks.

1. Direct comparison of EWSR1-FLI1’s suppressive effects on ATM activation/signaling with loss of canonical ATM activators to benchmark the effect size and demonstrate the biological significance of the (partial) ATM defects we report here.

Great list, would love to be added!