Carter, Daniel R., Murray, Jayne, Cheung, Belamy B., Gamble, Laura, Koach, Jessica, Tsang, Joanna, Sutton, Selina, Kalla, Heyam, Syed, Sarah, Gifford, Andrew J., Issaeva, Natalia ORCID: 0000-0001-5483-6610, Biktasova, Asel, Atmadibrata, Bernard, Sun, Yuting, Sokolowski, Nicolas, Ling, Dora, Kim, Patrick Y., Webber, Hannah, Clark, Ashleigh, Ruhle, Michelle, Liu, Bing, Oberthuer, Andre, Fischer, Matthias, Byrne, Jennifer, Saletta, Federica ORCID: 0000-0003-0598-3504, Thwe, Le Myo, Purmal, Andrei, Haderski, Gary, Burkhart, Catherine, Speleman, Frank, De Preter, Katleen, Beckers, Anneleen, Ziegler, David S., Liu, Tao ORCID: 0000-0001-6244-7316, Gurova, Katerina V., Gudkov, Andrei V., Norris, Murray D., Haber, Michelle ORCID: 0000-0003-2036-8817 and Marshall, Glenn M. (2015). Therapeutic targeting of the MYC signal by inhibition of histone chaperone FACT in neuroblastoma. Sci. Transl. Med., 7 (312). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1946-6242

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Carter, Daniel R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murray, JayneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheung, Belamy B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gamble, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koach, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tsang, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sutton, SelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kalla, HeyamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Syed, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gifford, Andrew J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Issaeva, NataliaUNSPECIFIEDorcid.org/0000-0001-5483-6610UNSPECIFIED
Biktasova, AselUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Atmadibrata, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, YutingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sokolowski, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ling, DoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kim, Patrick Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Webber, HannahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clark, AshleighUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruhle, MichelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, BingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oberthuer, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Byrne, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saletta, FedericaUNSPECIFIEDorcid.org/0000-0003-0598-3504UNSPECIFIED
Thwe, Le MyoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Purmal, AndreiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haderski, GaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burkhart, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speleman, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Preter, KatleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckers, AnneleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziegler, David S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, TaoUNSPECIFIEDorcid.org/0000-0001-6244-7316UNSPECIFIED
Gurova, Katerina V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gudkov, Andrei V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Norris, Murray D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haber, MichelleUNSPECIFIEDorcid.org/0000-0003-2036-8817UNSPECIFIED
Marshall, Glenn M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-387245
DOI: 10.1126/scitranslmed.aab1803
Journal or Publication Title: Sci. Transl. Med.
Volume: 7
Number: 312
Date: 2015
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1946-6242
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHROMATIN TRANSCRIPTION FACT; BET BROMODOMAIN INHIBITION; SPONTANEOUS REGRESSION; MALIGNANT PROGRESSION; TUMOR INITIATION; IN-VIVO; CANCER; P53; EXPRESSION; PROTEINMultiple languages
Cell Biology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38724

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