In vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer

Cited 0 time in scopus
Metadata Downloads
Title
In vitro evaluation of histone deacetylase inhibitors as combination agents for colorectal cancer
Author(s)
J C Kim; E S Shin; C W Kim; S A Roh; D H Cho; Y S Na; T W Kim; M B Kim; Y L Hyun; S Ro; Seon-Young KimYong Sung Kim
Bibliographic Citation
Anticancer Research, vol. 29, no. 8, pp. 3027-3034
Publication Year
2009
Abstract
Background: Our primary aim was to evaluate the additive efficacy of histone deacetylase inhibitors (HDACIs) in established treatment regimens for colorectal cancer in concurrence with identifying the clinicopathological markers significantly associated with tumor responsiveness. Patients and Methods: The chemosensitivities of 125 colorectal carcinomas to established regimens [FLOX (5-FU +leucovorin + oxaliplatin) and FLIRI (5-FU + leucovorin +irinotecan)], two biologically targeted drugs (avastin and erbitux), and two hydroxamic acid derivatives (vorinostat, SAHA?, and a novel candidate, CG2) were comparatively evaluated using an in vitro tumor response assay. Results: The response rates of tumors (inhibition rate ≥30% ) were significantly greater for FLOX and combinations (55.2-68%) compared to FLIRI and combinations (44-63.2% ) (p=0.001 to 0.048), except in the case of the CG2 combination. The additive effects of HDACIs on the respective established regimens were considerably greater for non-responsive tumors (64.3-80% ) than responsive tumors (32.7-45% ) (p≤0.0001 to 0.008). A number of biological parameters, including less advanced tumors and p53 overexpression, were significantly associated with additive chemosensitivity to HDACIs in combination with FLOX and FLIRI in multivariate analyses (p≤0.001 to 0.023). Expanding tumor growth, diffuse cytoplasmic carcinoembryonic antigen (CEA) expression and synchronous adenoma were associated with combination regimens with targeted drugs (p=0.013 to 0.032). Conclusion: Our findings show additive chemoresponsiveness of colorectal tumors to HDAC inhibitors in combination with established regimens. The significant parameters associated with combination regimens of targeted drugs and HDACIs may be applied as effective chemosensitive markers in future clinical trials.
Keyword
Histone deacetylase inhibitorcombinationchemosensitivityin vitro assaycolorectal adenocarcinomas
ISSN
0250-7005
Publisher
Int Inst Anticancer Research
Type
Article
Appears in Collections:
Korea Bioinformation Center > 1. Journal Articles
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.