Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma

  title={Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma},
  author={Daniel R. Carter and Jayne Murray and Belamy B. Cheung and Laura D. Gamble and Jessica Koach and Joanna Tsang and Selina K. Sutton and Heyam Kalla and Sarah Syed and Andrew J. Gifford and Natalia Issaeva and Asel K Biktasova and Bernard Atmadibrata and Yuting Liang Sun and Nicolas AS Sokolowski and Dora Ling and Patrick Y. Kim and Hannah T Webber and Ashleigh Clark and Michelle Ruhle and Bing Liu and Andr{\'e} Oberthuer and Matthias Hermann Fischer and Jennifer A. Byrne and Federica Saletta and Le Myo Thwe and Andrei A. Purmal and Gary J Haderski and Catherine A Burkhart and Frank Speleman and Katleen De Preter and Anneleen Beckers and David S Ziegler and Tao Liu and Katerina V Gurova and Andrei V. Gudkov and Murray D. Norris and Michelle Haber and Glenn M. Marshall},
  journal={Science Translational Medicine},
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… CONTINUE READING
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