EPEN-11. PROTEASOME AND HDAC INHIBITORS ARE CYTOTOXIC AGAINST RELA-FUSION PEDIATRIC EPENDYMOMA CELLS

• DOI: 10.1093/neuonc/noz036.068
• Publication Date: 2019-04-23T03:09:47Z
• Authors: Marissa Campagna; Xiangjuan Ma; Lauren McCarl; Rajeev Kumar; Alberto Broniscer; Sameer Agnihotri; James Felker; Ian Pollack; Gary Kohanbash
• Keywords: Panobinostat; Trichostatin A; Ependymoma; Cereblon; Histone deacetylase inhibitor

Ependymomas are the third most common pediatric brain tumor. Nine ependymoma subgroups have been described based on tumor location and genetics. Of supratentorial ependymomas, C11orf95-RELA fusion (ST-EPN-RELA) subgroup is aggressive. The RELA encoded protein an NF-κB transcription factor family member activates signaling. It has reported that other pathways important for ST-EPN-RELA tumors. We therefore hypothesized cells may be sensitive to signaling cascade inhibitors. To test our hypothesis we evaluated cytotoxicity of multiple NF-kB inhibitors DKFZ-EP1NS RELA-fusion positive established patient-derived line (CPITT-1). Cells were treated with a single drug or combinations drugs at concentrations ranging from 10 µM- 0.01 nM 3–4 days WST-1 assay was used assess viability. initially tested, Trichostatin A, histone deacetylase (HDAC) inhibitor, in combination MG-132, proteasome displayed highest level cytotocity against both lines. These findings led us clinically applicable drugs, including Marizomib, penetrant HDAC inhibitors, Panobinostat Valproic acid. For cells, IC50 Marizomib alone 40.82 nM, had 7.4 Acid 44.19. CPITT-1 25.8nM, 3.07 27.04 nM. Overall, observed highly toxic tested. Further studies warranted evaluate use these treating