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

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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.
Keywords
BET BROMODOMAIN INHIBITION, SPONTANEOUS REGRESSION, CHROMATIN TRANSCRIPTION FACT, MALIGNANT PROGRESSION, TUMOR INITIATION, IN-VIVO, CANCER, P53, EXPRESSION, PROTEIN

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Chicago
Carter, Daniel R, Jayne Murray, Belamy B Cheung, Laura Gamble, Jessica Koach, Joanna Tsang, Selina Sutton, et al. 2015. “Therapeutic Targeting of the MYC Signal by Inhibition of Histone Chaperone FACT in Neuroblastoma.” Science Translational Medicine 7 (312).
APA
Carter, D. R., Murray, J., Cheung, B. B., Gamble, L., Koach, J., Tsang, J., Sutton, S., et al. (2015). Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma. SCIENCE TRANSLATIONAL MEDICINE, 7(312).
Vancouver
1.
Carter DR, Murray J, Cheung BB, Gamble L, Koach J, Tsang J, et al. Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma. SCIENCE TRANSLATIONAL MEDICINE. 2015;7(312).
MLA
Carter, Daniel R, Jayne Murray, Belamy B Cheung, et al. “Therapeutic Targeting of the MYC Signal by Inhibition of Histone Chaperone FACT in Neuroblastoma.” SCIENCE TRANSLATIONAL MEDICINE 7.312 (2015): n. pag. Print.
@article{7040520,
  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.},
  articleno    = {312ra176},
  author       = {Carter, Daniel R and Murray, Jayne and Cheung, Belamy B and Gamble, Laura and Koach, Jessica and Tsang, Joanna and Sutton, Selina and Kalla, Heyam and Syed, Sarah and Gifford, Andrew J and Issaeva, Natalia and Biktasova, Asel and Atmadibrata, Bernard and Sun, Yuting and Sokolowski, Nicolas and Ling, Dora and Kim, Patrick Y and Webber, Hannah and Clark, Ashleigh and Ruhle, Michelle and Liu, Bing and Oberthuer, Andr{\'e} and Fischer, Matthias and Byrne, Jennifer and Saletta, Federica and Thwe, Le Myo and Purmal, Andrei and Haderski, Gary and Burkhart, Catherine and Speleman, Franki and De Preter, Katleen and Beckers, Anneleen and Ziegler, David S and Liu, Tao and Gurova, Katerina V and Gudkov, Andrei V and Norris, Murray D and Haber, Michelle and Marshall, Glenn M},
  issn         = {1946-6234},
  journal      = {SCIENCE TRANSLATIONAL MEDICINE},
  language     = {eng},
  number       = {312},
  pages        = {12},
  title        = {Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma},
  url          = {http://dx.doi.org/10.1126/scitranslmed.aab1803},
  volume       = {7},
  year         = {2015},
}

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