Lin Xiao, Klaartje Somers, Jayne Murray, Ruby Pandher, Mawar Karsa, Emma Ronca, Angelika Bongers, Rachael Terry, Anahid Ehteda, Laura D Gamble, Natalia Issaeva, Katerina I Leonova, Aisling O'Connor, Chelsea Mayoh, Pooja Venkat, Hazel Quek, Jennifer Brand, Frances K Kusuma, Jessica A Pettitt, Erin Mosmann, Adam Kearns, Georgina Eden, Stephanie Alfred, Sophie Allan, Lei Zhai, Alvin Kamili, Andrew J Gifford, Daniel R Carter, Michelle J Henderson, Jamie I Fletcher, Glenn Marshall, Ricky W Johnstone, Anthony J Cesare, David S Ziegler, Andrei V Gudkov, Katerina V Gurova, Murray D Norris, Michelle Haber
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 examine histone eviction, heterochromatin transcription, and chromatin compaction...
August 1, 2021: Clinical Cancer Research