ATRT-05. DNA DAMAGE REPAIR INHIBITOR LP-184 INHIBITS CELL GROWTH IN ATRT

Abstract Atypical teratoid rhabdoid tumor (ATRT) is a rare, aggressive pediatric brain tumor. It characterized by inactivation of SMARCB1 gene. There currently no standard care for treatment. LP-184 an analog acylfulvene. induces cell-cycle arrest and cell apoptosis through alkylation DNA RNA. Previously, was shown to have preclinical efficacy in temozolomide-resistant human glioblastoma lines. Additionally, it reported that loss SMARB1 increases sensitivity LP-184. Therefore, we hypothesized may be effective against ATRTs. We evaluated the effect multiple ATRT lines, including CHLA06, CHLA266, BT37. Treatment with showed inhibits growth from 10nM 200nM concentrations line (CellTiter Blue assay BT37 p<0.0001 t-test). identified IC50 23.92nM. induced 96 hours after treatment several lines as demonstrated immunofluorescence cleaved caspase-3 (CHLA06 p=0.0003 50nM vs DMSO, CHLA266 p=0.002 p=0.0014 DMSO t-test) Western blot c-PARP. decreased proliferation Bromodeoxyuridine (BrdU) p-RB. Further evaluations vitro vivo are underway. Our data so far suggests potential therapeutic option ATRT.