PLX167272

GSE137403: SWI/SNF inhibition leads to epigenetic reprogramming in rhabdoid tumor [RNA-seq]

  • Organsim human
  • Type RNASEQ
  • Target gene
  • Project ARCHS4

Rhabdoid tumor is a pediatric cancer characterized by the biallelic inactivation of SMARCB1, a subunit of the SWI/SNF chromatin remodeling complex. SMARCB1 inactivation leads to SWI/SNF redistribution to favor a proliferative dedifferentiated cellular state. Although this deletion is the known oncogenic driver, SWI/SNF therapeutic targeting remains a challenge. Here we show mithramycin and a second-generation analogue EC-8042 are effective in this tumor type. Mithramycin evicts SWI/SNF from chromatin triggering a cellular response characterized by chromatin compartment remodeling and promoter reprogramming. These effects lead to differentiation and marked xenograft tumor regressions in vivo. This study provides a therapeutic candidate for rhabdoid tumor and an approach that may be applicable to the more than 20% of cancers characterized by mutated SWI/SNF. SOURCE: Patrick Grohar (groharp@email.chop.edu) - Children's Hospital of Philadelphia

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