Identifying and targeting cancer-specific metabolism with network-based drug target prediction.
EBioMedicine
; 43: 98-106, 2019 May.
Article
en En
| MEDLINE
| ID: mdl-31126892
ABSTRACT
BACKGROUND:
Metabolic rewiring allows cancer cells to sustain high proliferation rates. Thus, targeting only the cancer-specific cellular metabolism will safeguard healthy tissues.METHODS:
We developed the very efficient FASTCORMICS RNA-seq workflow (rFASTCORMICS) to build 10,005 high-resolution metabolic models from the TCGA dataset to capture metabolic rewiring strategies in cancer cells. Colorectal cancer (CRC) was used as a test case for a repurposing workflow based on rFASTCORMICS.FINDINGS:
Alternative pathways that are not required for proliferation or survival tend to be shut down and, therefore, tumours display cancer-specific essential genes that are significantly enriched for known drug targets. We identified naftifine, ketoconazole, and mimosine as new potential CRC drugs, which were experimentally validated.INTERPRETATION:
The here presented rFASTCORMICS workflow successfully reconstructs a metabolic model based on RNA-seq data and successfully predicted drug targets and drugs not yet indicted for colorectal cancer. FUND This study was supported by the University of Luxembourg (IRP grant scheme; R-AGR-0755-12), the Luxembourg National Research Fund (FNR PRIDE PRIDE15/10675146/CANBIO), the Fondation Cancer (Luxembourg), the European Union's Horizon2020 research and innovation programme under the Marie Sklodowska- Curie grant agreement No 642295 (MEL-PLEX), and the German Federal Ministry of Education and Research (BMBF) within the project MelanomSensitivity (BMBF/BM/7643621).Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
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Biología Computacional
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Metabolismo Energético
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Descubrimiento de Drogas
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Terapia Molecular Dirigida
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
EBioMedicine
Año:
2019
Tipo del documento:
Article
País de afiliación:
Luxemburgo