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. 2011 Dec 1;106(1):77–84. doi: 10.1038/bjc.2011.527

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Copyright © 2012 Cancer Research UK

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(A) Proposed model of epigenetic modulation at RARβ gene loci. RARβ gene expression is silenced due to histone deacetylation, partial promoter methylation at the CpG islands and associated recruitment of the TAC, making the transcriptional site inaccessible and resistant to retinoid ligands. However, in the presence of HDAC inhibitors (HDACI), RARβ is re-expressed, and tumour cell sensitivity to retinoids is restored. (B) Treatment schema. Depicted is the schedule of administration of weekly oral entinostat at the starting dose of 4 mg m⁻² and daily oral CRA 1 mg kg⁻¹ for 21 days with 1-week rest. During Cycle 1, FNA was planned for accessible tumours at pre-treatment and day 22.