SIRT2 as an Epigenetic Vulnerability in Atypical Teratoid Rhabdoid Tumors
Abstract
While the importance of identifying new molecular targets for atypical teratoid rhabdoid tumor (ATRT) therapy has long been appreciated, progress has been limited. Conventional treatment strategies empirically using small-molecule inhibitors have failed to identify new therapeutic modalities. We applied an RNAi-mediated synthetic lethal screen to discover the epigenetic dependencies in ATRT and identified SIRT2 as a key regulator of viability in this tumor. Nothing is known about the role of SIRT2 in ATRT. This research is innovative because we propose for the first time that inhibition of SIRT2 is synthetic lethal with the SMARCB1 deletion in ATRT. We have obtained multiple ATRT cell lines and developed orthotopic xenograft models enabling this project to proceed. We have obtained several novel proprietary SIRT2 inhibitors to test as therapeutic agents. Our study will give a unique insight into the concept of targeting epigenetic regulators in treating ATRT.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810369
Entities
People
- Rajeev Vibhakar
Organizations
- United States Army
- University of Colorado Denver