The Jumonji-domain histone demethylase inhibitor JIB-04 deregulates oncogenic programs and increases DNA damage in Ewing Sarcoma, resulting in impaired cell proliferation and survival, and reduced tumor growth.

ABSTRACT: Ewing Sarcoma is an aggressive malignant neoplasm affecting children and young adults. Ewing Sarcoma is driven by transcription factor fusion oncoproteins, most commonly EWS/Fli1. While some patients can be cured with high-dose, multi-agent, chemotherapy, those that cannot currently have few options. Targeting of the driver oncofusion remains a logical therapeutic approach, but has proven difficult. Recent work has pointed to epigenetic mechanisms as key players, and potential new therapeutic targets, in Ewing Sarcoma. In this study we examined the activity of the pan-JHDM pharmacologic inhibitor JIB-04 in this disease. We show that JIB-04 potently inhibits the growth and viability of Ewing Sarcoma cells, and also impairs tumor xenograft growth. Effects on histone methylation at growth-inh

SUBMITTER: Parrish JK 

PROVIDER: S-EPMC6145692 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature