Comparison between Therapeutic Efficacies of Histone Deacetylase Inhibitors and Established Drug Regimens Against Breast Cancer Cells using the Histoculture Drug Response Assay.
10.4048/jbc.2009.12.4.241
- Author:
Jin Young SEO
1
;
Yoo Mi LEE
;
Dong Hyung CHO
;
Seon Ae ROH
;
Seong gu RO
;
Young Lan HYUN
;
Seon Young KIM
;
Youg Sung KIM
;
Tae Won KIM
;
Sei Hyun AHN
;
Jin Cheon KIM
Author Information
1. Department of Surgery, University of Ulsan College of Medicin, Seoul, Korea. jckim@amc.seoul.kr
- Publication Type:Original Article ; Clinical Trial
- Keywords:
Breast neoplasms, Chemosensitivity, Histone deacetylase inhibitor;
Histoculture drug response assay
- MeSH:
Biomarkers;
Breast;
Breast Neoplasms;
Cyclophosphamide;
Doxorubicin;
Gene Expression;
Histone Deacetylase Inhibitors;
Histone Deacetylases;
Histones;
Humans;
Hydroxamic Acids;
Mastectomy;
Nucleosomes;
Paclitaxel;
Sulfonamides;
Taxoids
- From:Journal of Breast Cancer
2009;12(4):241-248
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Histone deacetylase inhibitors (HDACIs) induce accumulation of acetylated histones in nucleosomes, which lead to reactivate gene expression and inhibit the growth and survival of tumor cells. This study evaluated the efficacy of HDACIs in breast cancer cells in comparison with other established drug regimens. METHODS: Drug responses of tumor samples from mastectomy specimens of 78 breast cancer patients were evaluated using the histoculture drug response assay (HDRA). Tumor inhibition rates (IRs) of established drug regimens such as doxorubicin, cyclophosphamide, doxorubicin with cyclophosphamide (AC), paclitaxel, docetaxel and doxorubicin with docetaxel (AT), as well as those of three HDACIs (SAHA, PXD101, and a novel compound CG-2) were evaluate. RESULTS: The percentages of chemosensitive tumors (chemoresponsiveness) were 26.9-60.3% with established regimens and 61.5-73.1% with HDACIs when the cutoff value for inhibition rate was set at 30%. Breast cancer cells appeared to be more chemoresponsive to HDACIs than to established drug regimens. Chemoresponsiveness to AT was the highest among the established drug regimens. A combination regimen offered higher activity than did a single drug (doxorubicin vs AT; p<0.001). HER2/Neu-overexpressing breast cancers were chemosensitive to SAHA and AT (p=0.031 and 0.04, respectively). CONCLUSION: Our findings show that breast cancer cells were sensitive to HDACIs, with therapeutic efficacies comparable to those of established drug regimens. Specific biological markers such as HER2/Neu could be assessed for effectiveness as HDACIs chemosensitivity markers in further clinical trials.
