Dual targeting of chromatin stability by the curaxin CBL0137 and histone deacetylase inhibitor panobinostat shows significant preclinical efficacy in neuroblastoma

L Xiao; K Somers; J Murray; R Pandher; M Karsa; E Ronca; A Bongers; R Terry; A Ehteda; LD Gamble; N Issaeva; KI Leonova; A O’Connor; C Mayoh; P Venkat; H Quek; J Brand; FK Kusuma; JA Pettitt; E Mosmann; A Kearns; G Eden; S Alfred; S Allan; L Zhai; A Kamili; AJ Gifford; DR Carter; MJ Henderson; JI Fletcher; G Marshall; RW Johnstone; AJ Cesare; DS Ziegler; AV Gudkov; KV Gurova; MD Norris; M Haber

Journal article

Dual targeting of chromatin stability by the curaxin CBL0137 and histone deacetylase inhibitor panobinostat shows significant preclinical efficacy in neuroblastoma

L Xiao, K Somers, J Murray, R Pandher, M Karsa, E Ronca, A Bongers, R Terry, A Ehteda, LD Gamble, N Issaeva, KI Leonova, A O’Connor, C Mayoh, P Venkat, H Quek, J Brand, FK Kusuma, JA Pettitt, E Mosmann Show all

Clinical Cancer Research | Published : 2021

DOI: 10.1158/1078-0432.CCR-20-2357

Abstract

Purpose: We investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma. Experimental Design: The effects of the drug combination on cancer growth were examined in vitro and in animal models of MYCN-amplified neuroblastoma. The molecular mechanisms of action were analyzed by multiple techniques including whole transcriptome profiling, immune deconvolution analysis, immunofluorescence, flow cytometry, pulsed-field gel electrophoresis, assays to assess cell growth and apoptosis, and a range of cell-based reporter systems to e..

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University of Melbourne Researchers

Ricky Johnstone Author

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Grants

Awarded by National Cancer Institute

Funding Acknowledgements

We would like to thank QIMR Histology Staining Facility, Garvan Histopathology Facility, the Animal Facility at Children's Cancer Institute, and Ramaciotti Centre for Genomics at UNSW, for providing technical assistance for this project. We thank Scott Page and the Australian Cancer Research Foundation Telomere Analysis Centre at the Children's Medical Research Institute (CMRI) for microscopy infrastructure. L. Xiao and E. Ronca are supported by a grant from Cancer Institute NSW (ECF171127) and philanthropy from Neuroblastoma Australia. K. Somers is supported by funding from the Kids Cancer Alliance (KCA). K. Somers, M. Karsa, A. Bongers, and M. Henderson are supported by funding from Tenix Foundation and Anthony Rothe Memorial Trust. D. Carter and L. Zhai are supported by grant (1123235) awarded through the Priority-driven Collaborative Cancer Research Scheme and cofunded by Cancer Australia and The Kids' Cancer Project. A. O'Connor and A. Cesare is supported by grants from the National Health and Medical Research Council (NHMRC; 1053195, 1106241, 1104461), and philanthropy from the Goodridge Foundation and Stanford Brown, Inc (Sydney, Australia). M. Haber and M. Norris are supported by grants from NHMRC (APP1132608 and APP1085411), Cancer Institute NSW (14/TPG/1-13), Cancer Council NSW (PG 16-01), Tour de Cure, and Neuroblastoma Australia.