Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma

Supratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that lead to chemoresistance traits of ST-RELA remain elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.

Citation:
de Almeida Magalhaes T, Alencastro Veiga Cruzeiro G, ……. Ancliffe M, Rodrigues da Silva K, Jiang L, Gojo J, Cherry Liu Y, Carline B, Kuchibhotla M, Pinto Saggioro F, …….. Endersby R, Filbin MG, Silva Borges K, et al. Activation of Hedgehog signaling by the oncogenic RELA fusion reveals a primary cilia-dependent vulnerability in supratentorial ependymoma. Neuro Oncol. 2023;25(1):185-98.

Keywords:
Alisertib; Hedgehog pathway; Primary cilia; ST-RELA ependymoma; Sonidegib

Abstract:
Supratentorial RELA fusion (ST-RELA) ependymomas (EPNs) are resistant tumors without an approved chemotherapeutic treatment. Unfortunately, the molecular mechanisms that lead to chemoresistance traits of ST-RELA remain elusive. The aim of this study was to assess RELA fusion-dependent signaling modules, specifically the role of the Hedgehog (Hh) pathway as a novel targetable vulnerability in ST-RELA.