Seclidemstat (SP-2577) Induces Transcriptomic Reprogramming and Cytotoxicity in Multiple Fusion-Positive Sarcomas.

ABSTRACT: Genes encoding the RNA-binding proteins FUS, EWSR1, and TAF15 (FET proteins) are involved in chromosomal translocations in rare sarcomas. The encoded fusion oncoproteins typically include a DNA-binding domain and function as oncogenic transcription factors. FET-rearranged sarcomas are often aggressive malignancies affecting patients of all ages. Oncogenic fusion transcription factors are challenging to target directly, and new therapies are needed. Treatment with the small molecule SP-2509 results in reversal of the transcriptional activity of the FET fusion that causes Ewing sarcoma, EWSR1::FLI1. A similar molecule, seclidemstat (SP-2577), is currently in clinical trials for FET-rearranged sarcomas (NCT03600649), but its pharmacologic activity in FET fusion-positive sarcomas has not been

SUBMITTER: Rask GC 

PROVIDER: S-EPMC12421227 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature