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Sensitization of (colon) cancer cells to death receptor related therapies A report from the FP6-ONCODEATH research consortium
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SYSNO ASEP 0387575 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Sensitization of (colon) cancer cells to death receptor related therapies A report from the FP6-ONCODEATH research consortium Author(s) Pintzas, A. (GR)
Zhivotovsky, B. (SE)
Workman, P. (GB)
Clarke, P.A. (GB)
Linardopoulos, S. (GB)
Martinou, J.C. (CH)
Lacal, J.C. (ES)
Robine, S. (FR)
Nasioulas, G. (GR)
Anděra, Ladislav (UMG-J) RIDSource Title Cancer Biology & Therapy - ISSN 1538-4047
Roč. 13, č. 7 (2012), s. 458-466Number of pages 9 s. Language eng - English Country US - United States Keywords cancer ; death receptors ; kinase inhibitors ; mitochondria ; targeted therapies Subject RIV EB - Genetics ; Molecular Biology Institutional support UMG-J - RVO:68378050 UT WOS 000303927700002 DOI 10.4161/cbt.19600 Annotation The objective of the ONCODEATH consortium [EU Research Consortium "ONCODEATH" (2006-2010)] was to achieve sensitization of solid tumor cells to death receptor related therapies using rational mechanism-based drug combinations of targeted therapies. In this collaborative effort, during a period of 42 months, cell and animal model systems of defined oncogenes were generated. Exploitation of generated knowledge and tools enabled the consortium to achieve the following research objectives: (1) elucidation of tumor components which confer sensitivity or resistance to TRAIL-induced cell death; (2) providing detailed knowledge on how small molecule Hsp90, Aurora, choline kinase, BRAF inhibitors, DNA damaging agents, HDAC and DNMT inhibitors affect the intrinsic apoptotic amplification and execution machineries; (3) optimization of combined action of TRAIL with these therapeutics for optimum effects with minimum concentrations and toxicity in vivo. These findings provide mechanistic basis for a pharmacogenomic approach, which could be exploited further therapeutically, in order to reach novel personalized therapies for cancer patients. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2013
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