Journal
CANCER BIOLOGY & THERAPY
Volume 13, Issue 7, Pages 458-466Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.19600
Keywords
cancer; death receptors; kinase inhibitors; mitochondria; oncogenes; targeted therapies; rational combinations
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Funding
- EU [LSHC-CT-2006-037278 ONCODEATH]
- Cancer Research UK [11566] Funding Source: researchfish
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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.
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