Title: Novel drug candidates for the treatment of metastatic colorectal cancer through global inverse gene-expression profiling
Authors: van Noort, Vera ×
Schölch, Sebastian
Iskar, Murat
Zeller, Georg
Ostertag, Kristina
Schweitzer, Christine
Werner, Kristin
Weitz, Jürgen
Koch, Moritz
Bork, Peer #
Issue Date: Oct-2014
Publisher: Waverly Press
Series Title: Cancer Research vol:74 issue:20 pages:5690-5699
Article number: 10.1158/0008-5472.CAN-13-3540
Abstract: Drug-induced gene-expression profiles that invert disease profiles have recently been illustrated to be a starting point for drug repositioning. In this study, we validate this approach and focus on prediction of novel drugs for colorectal cancer, for which there is a pressing need to find novel antimetastatic compounds. We computationally predicted three novel and still unknown compounds against colorectal cancer: citalopram (an antidepressant), troglitazone (an antidiabetic), and enilconazole (a fungicide). We verified the compounds by in vitro assays of clonogenic survival, proliferation, and migration and in a subcutaneous mouse model. We found evidence that the mode of action of these compounds may be through inhibition of TGFβ signaling. Furthermore, one compound, citalopram, reduced tumor size as well as the number of circulating tumor cells and metastases in an orthotopic mouse model of colorectal cancer. This study proposes citalopram as a potential therapeutic option for patients with colorectal cancer, illustrating the potential of systems pharmacology.
ISSN: 0008-5472
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Centre of Microbial and Plant Genetics
× corresponding author
# (joint) last author

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