Prostate cancer is one of the leading causes of death from cancer in men.
Several prognostic factors allow differentiating low-grade and high-grade tumors with high metastatic potential. High-grade tumors are currently treated with hormone therapy, to which taxanes are added when they become resistant to castration. Clinical trials with other anticancer agents never took into account the genetic background of these tumors and most of them have provided low response rates. Here, we used an in silico approach to screen for drug candidates that could be used as an alternative to taxanes, based on a published expression signature of 86 genes that can distinguish high-grade from low-grade tumors [True et al, PNAS 2006 103:10991-6]. We explored the NCI databases, which allow access to both gene expression profiles of 60 human tumor cell lines and their in vitro sensitivity to anticancer drugs, and identified several genes in this signature whose expression levels were correlated to chemosensitivity. As a validation example of this in silico approach, we report a set of 6 genes, whose expression can predict cell sensitivity to oxaliplatin but not to cisplatin. This signature was validated in vitro by silencing these genes in DU145, LNCaP, C4-2B prostate cancer cells, which was accompanied by an alteration of oxaliplatin, but not cisplatin cytotoxicity. These results demonstrate the relevance of our approach for the identification of both alternative therapies in the treatment of high-grade prostate cancers and new biomarkers to predict tumor response in the clinic.
Written by:
Puyo S, Houede N, Kauffmann A, Richaud P, Robert J, Pourquier P. Are you the author?
1 INSERM U916 & Universite de Bordeaux.
Reference: Mol Pharmacol. 2012 Sep 17. Epub ahead of print.
doi: 10.1124/mol.112.080333
PubMed Abstract
PMID: 22986617
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