In vitro chemosensitivity of gastric adenocarcinomas to histone deacetylase inhibitors, compared to established drugs

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Title
In vitro chemosensitivity of gastric adenocarcinomas to histone deacetylase inhibitors, compared to established drugs
Author(s)
S N Yoon; S A Roh; D H Cho; M B Kim; Y L Hyun; S Ro; B S Kim; Seon-Young Kim; Yong Sung Kim; J C Kim
Bibliographic Citation
Hepato-Gastroenterology, vol. 57, no. 99, pp. 657-662
Publication Year
2010
Abstract
BACKGROUND/AIMS: This study was performed to determine the efficacy of histone deacetylase inhibitors in gastric cancer, together with other established regimens. METHODOLOGY: The chemosensitivities of 93 gastric cancer patients to established drugs, and three histone deacetylase inhibitors (SAHA, PXD101, and a novel candidate, CG-2) were evaluated using the histoculture drug response assay. RESULTS: Tumor growth inhibition rates were the highest with cisplatin, followed by PXD101, taxol, docetaxel, and TS-1, in descending order. The response rates were 41.9-68.8%, and 37.6-47.3%, respectively, at an inhibition rate cutoff value of 30%. Synergistic activity was evident with most combinations of established drugs and histone deacetylase inhibitors. Diffuse- or mixed-type carcinomas on Lauren classification were closely associated with increased chemosensitivity to TS-1 (p = 0.044). Node-positive and "other than tubular type" tumors on WHO classification were chemosensitive to cisplatin (p = 0.011 and 0.014, respectively). CG-2 chemosensitivity was markedly associated with low preoperative CA72-4 level (≤4 U/ml) (p = 0.046). CONCLUSIONS: This in vitro chemosensitivity assay validates the comparable chemo-response of gastric cancers to histone deacetylase inhibitors and established drugs, indicating considerable therapeutic efficacy of these agents. Additionally, a number of clinicopathological parameters are significantly associated with specific regimens.
Keyword
ChemosensitivityGastric adenocarcinomasHistoculture drug response assay (HDRA)Histone deacetylase inhibitor
ISSN
0172-6390
Publisher
Hge Update Medical Publishing Sa
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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