Naslov
An expression-guided screen for small molecules targeting aggressive prostate cancer.

Autori
Patrick Mullane , Yukan Duan , Benjamin Benzon , Brian Simons , Paula Hurley , Zhenhua HuangLuigi Marchionni , Ismael A. Vergara , Mohammed Alshalalfa , Elai Davicioni , Edward M. Schaeffer , Ashley Ross

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Journal of Clinical Oncology / - , 2014

Skup
2014 ASCO Annual Meeting I

Mjesto i datum
Chicago (IL), Sjedinjene Američke Države, 30.05.2014. - 03.06.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
prostate cancer, druggable targets

Sažetak
Background: Though about half of newly diagnosed prostate cancer may not require immediate treatment, it remains the second most common cause of cancer death in the United States indicating a need for novel preventive and therapeutic treatments. Here we use expression based analysis to identify “druggable” targets which were then used to tailor screens for commercially available candidate inhibitors of prostate cancer. Methods: A list of 537 differentially expressed genes was developed by comparing expression profiles of prostate cancer from men with high risk localized disease that either metastasized or was cured following radical prostatectomy. Differentially expressed genes were compared to PharmGKB and Drugbank to link them to commercially available drugs. Identified drugs were assessed for their effects on cell viability, migration and invasion in androgen responsive and independent prostate cancer cell lines and in an ex-vivo embryonic development assay of prostate epithelial invasion. Results: Putative prostate cancer inhibitors roughly grouped into anti-neoplastic agents, tyrosine kinase inhibitors, statins, beta- blockers/beta-agonists, aldosterone/ATII inhibitors, catecholamine pathway related drugs, anti-platelets, immunosuppresants, leukotriene antagonists and anti-diabetic drugs. Multiple classes of drugs inhibited cell viability in a dose-dependent manner in prostate cancer cell lines with individual inhibitors in each group having disparate effects. A subset of drugs showed significant inhibition of cell migration, including Celecoxib, Metformin, Simvastatin, Iressa and Sunitinib. In addition, inhibition of prostate cell invasion into the surrounding mesenchyme was seen with several agents including Sorafenib and Metformin. Conclusions: Use of gene expression data and bioinformatics allowed for smaller scale screening of inhibitors enriched for putative effects on prostate cancer. Through these methods we identified inhibitors already shown to effect prostate cancer and in addition currently available drugs with previously unknown effects on prostate cancer.

Izvorni jezik
Engleski

POVEZANOST RADA