biostudies-literatureUnknownRask GCNCI NIH HHSGenes encoding the RNA-binding proteins FUS, EWSR1, and TAF15 (FET proteins) are involved in chromosomal translocations in rare sarcomas. FET-rearranged sarcomas are often aggressive malignancies affecting patients of all ages. New therapies are needed. These translocations fuse the 5' portion of the FET gene with a 3' partner gene encoding a transcription factor (TF). The resulting fusion proteins are oncogenic TFs with a FET protein low complexity domain (LCD) and a DNA binding domain. FET fusion proteins have proven stubbornly difficult to target directly and promising strategies target critical co-regulators. One candidate is lysine specific demethylase 1 (LSD1). LSD1 is recruited by multiple FET fusions, including EWSR1::FLI1. LSD1 promotes EWSR1::FLI1 activity and treatment with the bioRxiv : the preprint server for biology2024.05.19.594897https://www.ebi.ac.uk/biostudies/studies/S-EPMC11142045biostudies-literatureSeclidemstat blocks the transcriptional function of multiple FET-fusion oncoproteins.PMC11142045T32 CA269052Cannon MVTaslim CTheisen ERBayanjargal ASelich-Anderson JDuncan ACrow JCRask GCfalseSeclidemstat blocks the transcriptional function of multiple FET-fusion oncoproteins.Genes encoding the RNA-binding proteins FUS, EWSR1, and TAF15 (FET proteins) are involved in chromosomal translocations in rare sarcomas. FET-rearranged sarcomas are often aggressive malignancies affecting patients of all ages. New therapies are needed. These translocations fuse the 5' portion of the FET gene with a 3' partner gene encoding a transcription factor (TF). The resulting fusion proteins are oncogenic TFs with a FET protein low complexity domain (LCD) and a DNA binding domain. FET fusion proteins have proven stubbornly difficult to target directly and promising strategies target critical co-regulators. One candidate is lysine specific demethylase 1 (LSD1). LSD1 is recruited by multiple FET fusions, including EWSR1::FLI1. LSD1 promotes EWSR1::FLI1 activity and treatment with the 2024-01-01T00:00:00Z2024 May2026-05-29T03:15:03.065Z2026-05-29T03:06:41.893ZS-EPMC111420453882633010.1101/2024.05.19.594897