In vitro chemosensitivity of gastric adenocarcinomas to histone deacetylase inhibitors, compared to established drugs.
OBJECTIVE
This study was performed to determine the efficacy of histone deacetylase inhibitors in gastric cancer, together with other established regimens.


METHODS
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 CA724 level (< or = 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.
Yoon
Sang Nam
SN
Department of Surgery and Institute of Innovative Cancer Research, University of Ulsan College of Medicine and Asan Medical Center, 388-1 Poongnap-2-Dong Songpa-Ku, Seoul 138-736, Republic of Korea.
Roh
Seon Ae
SA
Cho
Dong Hyung
DH
Kim
Moon Bo
MB
Hyun
Young-Lan
YL
Ro
Seonggu
S
Kim
Byung Sik
BS
Kim
Seon Young
SY
Kim
Yong Sung
YS
Kim
Jin Cheon
JC
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
D056572:Histone Deacetylase Inhibitors