In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 8, No. 12_Supplement ( 2009-12-10), p. C163-C163
Abstract:
Gene-expression profiling has been applied in specific settings such as to elucidate the mechanisms of biological pathways, to classify subtypes of a disease, and to predict cancer prognosis. Furthermore, the Connectivity Map using gene-expression signature can categorize the biological responses to a large number of diverse small molecule therapeutics. To find new agents targeting gastric cancer, we analyzed global human gastric cancer gene expression profile using the Connectivity Map. From 3360 gastric cancer specific genes, it was revealed that the candidate compounds for targeting gastric cancer were histone deacetylase inhibitors (HDACi) such as vorinostat. We validated the therapeutic efficacy of vorinostat in gastric cancer cell lines. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines, but showed a different pattern in each cell line. Pharmacological or genetic inhibition of autophagy respectively by chloroquine and a siRNA against Beclin 1 increased the therapeutic efficacy of vorinostat, indicating a mechanism of drug resistance. Further transcriptome analysis will make it possible to find a predictive biomarker gene signature for vorinostat and as such can help in the future to better understand the action mechanisms of vorinostat. In conclusion, we showed that systems analysis using Connectivity Map with a human gastric cancer gene signature can be novel approach to find targeting agents for gastric cancer. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C163.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-09-C163
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2009
detail.hit.zdb_id:
2062135-8
SSG:
12
