| Literature DB >> 26537256 |
Daniel R Carter1, Jayne Murray2, Belamy B Cheung1, Laura Gamble2, Jessica Koach2, Joanna Tsang2, Selina Sutton2, Heyam Kalla2, Sarah Syed2, Andrew J Gifford3, Natalia Issaeva4, Asel Biktasova4, Bernard Atmadibrata2, Yuting Sun2, Nicolas Sokolowski2, Dora Ling2, Patrick Y Kim2, Hannah Webber2, Ashleigh Clark2, Michelle Ruhle2, Bing Liu2, André Oberthuer5, Matthias Fischer6, Jennifer Byrne7, Federica Saletta8, Le Myo Thwe7, Andrei Purmal9, Gary Haderski10, Catherine Burkhart10, Frank Speleman11, Katleen De Preter11, Anneleen Beckers11, David S Ziegler12, Tao Liu11, Katerina V Gurova13, Andrei V Gudkov13, Murray D Norris14, Michelle Haber15, Glenn M Marshall16.
Abstract
Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. We used a MYC target gene signature that predicts poor neuroblastoma prognosis to identify the histone chaperone FACT (facilitates chromatin transcription) as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small-molecule curaxin compound CBL0137 markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with standard chemotherapy by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN-amplified neuroblastoma cells and suggesting a treatment strategy for MYCN-driven neuroblastoma.Entities:
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Year: 2015 PMID： 26537256 PMCID： PMC6207083 DOI： 10.1126/scitranslmed.aab1803
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956