Sensitization of (colon) cancer cells to death receptor related therapies A report from the FP6-ONCODEATH research consortium

0387575 - ÚMG 2013 RIV US eng J - Journal Article
Pintzas, A. - Zhivotovsky, B. - Workman, P. - Clarke, P.A. - Linardopoulos, S. - Martinou, J.C. - Lacal, J.C. - Robine, S. - Nasioulas, G. - Anděra, Ladislav
Sensitization of (colon) cancer cells to death receptor related therapies A report from the FP6-ONCODEATH research consortium.
Cancer Biology & Therapy. Roč. 13, č. 7 (2012), s. 458-466. ISSN 1538-4047. E-ISSN 1555-8576
Grant - others:EK(XE) LSHC-CT-2006-037278
Institutional support: RVO:68378050
Keywords : cancer * death receptors * kinase inhibitors * mitochondria * targeted therapies
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.287, year: 2012

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.
Permanent Link: http://hdl.handle.net/11104/0218644