Sensitization of (colon) cancer cells to death receptor related therapies: a report from the FP6-ONCODEATH research consortium.
Cancer Biol Ther
; 13(7): 458-66, 2012 May.
Article
in En
| MEDLINE
| ID: mdl-22406997
ABSTRACT
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 mo, 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colonic Neoplasms
/
Receptors, Death Domain
/
Molecular Targeted Therapy
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Biol Ther
Journal subject:
NEOPLASIAS
/
TERAPEUTICA
Year:
2012
Document type:
Article
Affiliation country:
Greece