2012
DOI: 10.1002/hep.25566
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Abstract: Hepatocellular carcinoma (HCC) is a particularly lethal form of cancer, yet effective therapeutic options for advanced HCC are limited. As poly(ADP-ribose) polymerases (PARPs) and histone deacetylases (HDACs) are emerging to be among the most promising targets in cancer therapy, and sensitivity to PARP inhibition depends on homologous recombination (HR) deficiency and inhibition of HDAC activity blocks the HR pathway, we tested the hypothesis that co-targeting both enzymatic activities could synergistically in… Show more

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Cited by 34 publications
(28 citation statements)
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“…SBHA treatment suppressed the HpSC-HCC stemness traits with a reduction in the number of EpCAM + cells, and AG-014699 treatment further suppresses the recruitment of CHD4 during the DNA damage response. A recent study has shown that a combination therapy of HDAC and PARP inhibitors is effective for treating HCC [39], and our findings provide mechanistic insights into how HDAC and PARP inhibitors work to eradicate EpCAM + liver CSCs. The safety, tolerability, and efficacy of this combination therapy for HCC patients warrants further investigation in a clinical setting.…”
Section: Discussionmentioning
confidence: 52%
“…SBHA treatment suppressed the HpSC-HCC stemness traits with a reduction in the number of EpCAM + cells, and AG-014699 treatment further suppresses the recruitment of CHD4 during the DNA damage response. A recent study has shown that a combination therapy of HDAC and PARP inhibitors is effective for treating HCC [39], and our findings provide mechanistic insights into how HDAC and PARP inhibitors work to eradicate EpCAM + liver CSCs. The safety, tolerability, and efficacy of this combination therapy for HCC patients warrants further investigation in a clinical setting.…”
Section: Discussionmentioning
confidence: 52%
“…Aberrant amplification/overexpression of ALC1 is present in about 50% of all HCC cases and ALC1-overexpressing cells exhibit increased colony formation in soft agar and increased tumorigenicity in nude mice. 3 HepG2, shown by Zhang et al 1 to be the most responsive cell line to SAHA and olaparib, display much higher ALC1 expression than human HCC tissue. 3 It would be interesting to see if the two cell lines described by Zhang et al express ALC1 and at which levels, and to what extent findings with olaparib are exploitable by clinics in the half of HCC cases that are ALC1 negative.…”
Section: Targeting Chromatin Remodelers To Treat Hepatocellular Carcimentioning
confidence: 84%
“…We read with great interest the article by Zhang et al 1 in which the authors demonstrate that pharmacological targeting of the chromatin remodeling enzymes histone deacetylases (HDAC) and poly (ADP-ribose) polymerases inhibit hepatocellular carcinoma (HCC) cell growth. The authors showed that HCC cells display differential sensitivity to the HDAC inhibitor SAHA and PARP inhibitor olaparib, and identified two cell lines with sensitive versus resistant phenotype to both enzyme inhibitors, respectively.…”
Section: Targeting Chromatin Remodelers To Treat Hepatocellular Carcimentioning
confidence: 99%
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