title: Sensitization of (colon) cancer cells to death receptor related therapies: a report from the FP6-ONCODEATH research consortium.
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.
authors.affiliation: Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pintzas
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
authors.forename: Paul
authors.initials: P
authors.lastname: Workman
authors.forename: Paul A
authors.initials: PA
authors.lastname: Clarke
authors.forename: Spiros
authors.initials: S
authors.lastname: Linardopoulos
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lacal
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
authors.forename: George
authors.initials: G
authors.lastname: Nasioulas
authors.forename: Ladislav
authors.initials: L
authors.lastname: Andera
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D058990:Molecular Targeted Therapy; D053218:Receptors, Death Domain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D053218:Receptors, Death Domain