Targeting MYCN-driven transcription by BET-bromodomain inhibition

Clinical Cancer Research

Volumn 22, Issue 10, 2016, Pages 2470-2781

  Henssen, Anton ^a,b   Althoff, Kristina ^b,c   Odersky, Andrea ^b   Beckers, Anneleen ^d   Koche, Richard ^a   Speleman, Frank ^d   Schäfers, Simon ^b,c   Bell, Emma ^e   Nortmeyer, Maike ^e   Westermann, Frank ^e   De Preter, Katleen ^d   Florin, Alexandra ^f   Heukamp, Lukas ^g,h   Spruessel, Annika ^b   Astrahanseff, Kathy ⁱ   Lindner, Sven ^b   Sadowski, Natalie ^b   Schramm, Alexander ^b   Astorgues Xerri, Lucile ^j   Riveiro, Maria E ^j   Eggert, Angelika ⁱ   Cvitkovic, Esteban ^j,k   Schulte, Johannes H ^b,c,e,l   more..

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b UNIVERSITY HOSPITAL ESSEN   (Germany)

^c German Consortium for Translational Cancer Research (DKTK)   (Germany)

^d GHENT UNIVERSITY HOSPITAL   (Belgium)

^e GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^f UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^g NEO New Oncology GmbH   (Germany)

^h Institut für Hämatopathologie Hamburg   (Germany)

ⁱ CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^j Oncology Therapeutic Development   (France)

^k Oncoethix ^*  (Switzerland)

^l UNIVERSITY OF DUISBURG ESSEN   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 CHLOROPHENYL) N (4 HYDROXYPHENYL) 2,3,9 TRIMETHYL 6H THIENO[3,2 F][1,2,4]TRIAZOLO[4,3 A][1,4]DIAZEPINE 6 ACETAMIDE; PEPTIDES AND PROTEINS; PROTEIN BRD4; UNCLASSIFIED DRUG; ACETANILIDE DERIVATIVE; ANTINEOPLASTIC AGENT; BIRABRESIB; FUSED HETEROCYCLIC RINGS; N MYC PROTO ONCOGENE PROTEIN; NERVE PROTEIN; NUCLEAR PROTEIN; TRANSCRIPTION FACTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; CANCER CHEMOTHERAPY; CANCER INHIBITION; CELL CYCLE ARREST; CHROMATIN; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DNA SEQUENCE; DRUG EFFICACY; DRUG STRUCTURE; ENHANCER REGION; FEMALE; GENE; GENE AMPLIFICATION; GENE EXPRESSION; GENE REPRESSION; GENETIC TRANSCRIPTION; HISTONE ACETYLATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOLECULARLY TARGETED THERAPY; MOUSE; MYCN GENE; NEUROBLASTOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; DRUG EFFECTS; METABOLISM; NUDE MOUSE; TUMOR CELL LINE;

ACETANILIDES; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE; CELL LINE, TUMOR; FEMALE; GENE EXPRESSION; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; MICE; MICE, NUDE; N-MYC PROTO-ONCOGENE PROTEIN; NERVE TISSUE PROTEINS; NEUROBLASTOMA; NUCLEAR PROTEINS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 84969246399     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-1449     Document Type: Article

References (40)

1. Loven J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013;153:320-34.
2. Kouskouti A, Talianidis I. Histone modifications defining active genes persist after transcriptional and mitotic inactivation. EMBO J 2005;24: 347-57.
3. Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146:904-17.
4. Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, et al. Selective inhibition of BET bromodomains. Nature 2010;468:1067-73.
5. Sims RJ III, Belotserkovskaya R, Reinberg D. Elongation by RNA polymerase II: the short and long of it. Genes Dev 2004;18:2437-68.
6. Yang Z, He N, Zhou Q. Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol Cell Biol 2008;28:967-76.
7. Dey A, Nishiyama A, Karpova T, McNally J, Ozato K. Brd4 marks select genes on mitotic chromatin and directs postmitotic transcription. Mol Biol Cell 2009;20:4899-909.
8. Cheung NK, Dyer MA. Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer 2013;13:397-411.
9. Simon T, Berthold F, Borkhardt A, Kremens B, De Carolis B, Hero B. Treatment and outcomes of patients with relapsed, high-risk neuroblastoma: results of German trials. Pediatr Blood Cancer 2011;56:578-83.
10. Molenaar JJ, Domingo-Fernandez R, Ebus ME, Lindner S, Koster J, Drabek K, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet 2012;44:1199-206.
11. Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, et al. Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov 2013;3:308-23.
12. Althoff K, Beckers A, Bell E, Nortmeyer M, Thor T, Sprussel A, et al. A Creconditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene 2014;34:3357-68.
13. Noel JK, Iwata K, Ooike S, Sugahara K, Nakamura H, Daibata M. Development of the BET bromodomain inhibitor OTX015 [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR. Abstract nr C244.
14. Coude MM, Braun T, Berrou J, Dupont M, Bertrand S, Masse A, et al. BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells. Oncotarget 2015;6:17698-712.
15. Boi M, Gaudio E, Bonetti P, Kwee I, Bernasconi E, Tarantelli C, et al. The BET bromodomain inhibitor OTX015 affects pathogenetic pathways in preclinical B-cell tumor models and synergizes with targeted drugs. Clin Cancer Res 2015;21:1628-38.
16. Herait P, Berthon C, Thieblemont C, Raffoux E, Magarotto V, Stathis A, et al. BET-bromodomain inhibitor OTX015 shows clinically meaningful activity at nontoxic doses: interim results of an ongoing phase I trial in hematologic malignancies [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR. Abstract nr CT231.
17. Odore E, Rezai K, Riveiro E, Bourdel F, Herait P, Cvitkovic E, et al. A phase I pharmacokinetic study of OTX015 for the treatment of patients with hematologic malignancies. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR. Abstract nr LB-231.
18. Odore E, Lokiec F, Cvitkovic E, Bekradda M, Herait P, Bourdel F, et al. Phase I population pharmacokinetic assessment of the oral bromodomain inhibitor OTX015 in patients with haematologic malignancies. Clin Pharmacokinet. 2015 Sep 4. [Epub ahead of print].
19. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 2004;5:R80.
20. Hong F, Breitling R, McEntee CW, Wittner BS, Nemhauser JL, Chory J. RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis. Bioinformatics 2006;22:2825-7.
21. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005;102:15545-50.
22. Fredlund E, Ringner M, Maris JM, Pahlman S. High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma. Proc Natl Acad Sci USA 2008;105:14094-9.
23. Westermann F, Muth D, Benner A, Bauer T, Henrich KO, Oberthuer A, et al. Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. Genome Biol 2008;9:R150.
24. Zeller KI, Zhao X, Lee CW, Chiu KP, Yao F, Yustein JT, et al. Global mapping of c-Myc binding sites and target gene networks in human B cells. Proc Natl Acad Sci USA 2006;103:17834-9.
25. Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 2010;26:841-2.
26. Mochizuki K, Nishiyama A, Jang MK, Dey A, Ghosh A, Tamura T, et al. The bromodomain protein Brd4 stimulates G1 gene transcription and promotes progression to S phase. J Biol Chem 2008;283:9040-8.
27. Valentijn LJ, Koster J, Haneveld F, Aissa RA, van Sluis P, Broekmans ME, et al. Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification. Proc Natl Acad Sci U S A 2012;109: 19190-5.
28. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol 2008;9:R137.
29. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 2013;153:307-19.
30. Heukamp LC, Thor T, Schramm A, De Preter K, Kumps C, De Wilde B, et al. Targeted expression of mutated ALK induces neuroblastoma in transgenic mice. Sci Transl Med 2012;4:141ra91.
31. Pui CH, Gajjar AJ, Kane JR, Qaddoumi IA, Pappo ASMedscape. Challenging issues in pediatric oncology. Nat Rev Clin Oncol 2011;8:540-9.
32. McNeil DE, Cote TR, Clegg L, Rorke LB. Incidence and trends in pediatric malignancies medulloblastoma/primitive neuroectodermal tumor: a SEER update. Surveillance Epidemiology and End Results. Med Pediatr Oncol 2002;39:190-4.
33. Gustafson WC, Meyerowitz JG, Nekritz EA, Chen J, Benes C, Charron E, et al. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell 2014;26:414-27.
34. Brockmann M, Poon E, Berry T, Carstensen A, Deubzer HE, Rycak L, et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell 2013;24:75-89.
35. Berry T, Luther W, Bhatnagar N, Jamin Y, Poon E, Sanda T, et al. The ALK (F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 2012;22:117-30.
36. Umapathy G, El Wakil A, Witek B, Chesler L, Danielson L, Deng X, et al. The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma. Sci Signal 2014;7:ra102.
37. Chipumuro E, Marco E, Christensen CL, Kwiatkowski N, Zhang T, Hatheway CM, et al. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell 2014;159:1126-39.
38. Barone G, Anderson J, Pearson AD, Petrie K, Chesler L. New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK. Clin Cancer Res 2013;19:5814-21.
39. Mertz JA, Conery AR, Bryant BM, Sandy P, Balasubramanian S, Mele DA, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A 2011;108:16669-74.
40. Gargano B, Amente S, Majello B, Lania L. P-TEFb is a crucial co-factor for Myc transactivation. Cell Cycle 2007;6:2031-7.