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| Status |
Public on Mar 06, 2017 |
| Title |
A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Approved drugs are invaluable tools to study biochemical pathways and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here, we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered the synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these two drugs modulates the stability of the androgen receptor (AR) and resensitizes AR mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for γ-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC might be repurposed to tackle resistance to antiandrogens in prostate cancer patients.
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| Overall design |
Two biological replicates were produced for each condition. Drug treatment was compared to vehicle-treated cells.
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| Contributor(s) |
Licciardello MP, Ringler A, Markt P, Klepsch F, Lardeau C, Sdelci S, Schirghuber E, Müller AC, Caldera M, Wagner A, Herzog R, Penz T, Schuster M, Boidol B, Dürnberger G, Folkvaljon Y, Stattin P, Ivanov V, Colinge J, Bock C, Kratochwill K, Menche J, Bennett KL, Kubicek S |
| Citation(s) |
28530711 |
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| Submission date |
Feb 10, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Marco Paolo Licciardello |
| E-mail(s) |
marco.licciardello@icr.ac.uk
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| Organization name |
The Institute of Cancer Research
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| Street address |
15 Cotswold Road
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| City |
London |
| ZIP/Postal code |
SM2 5NG |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA374038 |
| SRA |
SRP099217 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE94783_rnaseq_process_cuffdiff_global_DMSO_Flut_PPC_genes_diff.tsv.gz |
3.0 Mb |
(ftp)(http) |
TSV |
| GSE94783_rnaseq_process_cuffdiff_global_DMSO_Flut_genes_diff.tsv.gz |
3.0 Mb |
(ftp)(http) |
TSV |
| GSE94783_rnaseq_process_cuffdiff_global_DMSO_PPC_genes_diff.tsv.gz |
3.0 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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