Final Report Summary - EPITRON (Epigenetic treatment of neoplastic disease)
The ultimate aim of the EPITRON project was to define and validate the concept of epigenetic treatment of cancer. In order to achieve it the project consortium focused on:
- providing a molecular understanding of the genome-wide genetic and epigenetic consequences of the formation of oncofusion proteins in Acute myeloid leukemia (AML);
- revealing the molecular mechanism of the anti-leukemic and anti-cancer action of epi-drugs;
- revealing the basis of the tumour-selective action of the TNF-related apoptosis-inducing ligand (TRAIL) signalling pathway that is activated by epi-drugs, nuclear receptor ligands and interferons;
- establishing mouse models to test the spectrum of anticancer actions of TRAIL in vivo and define in vivo toxicities;
- establishing mouse models that faithfully report the activation of (cancer cell-selective) anti-tumour pathways;
- synthesising and validating novel epi-drugs;
- verifying the concept of drug sensitisation by signalling crosstalk;
- establishing novel models to study epi-drugs in solid tumours
By dint of the multi-disciplinary nature of the consortium, an entire pipeline to accomplish these goals was established and in addition to the strong fundamental basis in basic research, the team's expertise included drug design and synthesis, whole-genome approaches and high-throughput screening, clinical interface, as well as the development and use of mouse models which accurately reproduce the human disease.
- providing a molecular understanding of the genome-wide genetic and epigenetic consequences of the formation of oncofusion proteins in Acute myeloid leukemia (AML);
- revealing the molecular mechanism of the anti-leukemic and anti-cancer action of epi-drugs;
- revealing the basis of the tumour-selective action of the TNF-related apoptosis-inducing ligand (TRAIL) signalling pathway that is activated by epi-drugs, nuclear receptor ligands and interferons;
- establishing mouse models to test the spectrum of anticancer actions of TRAIL in vivo and define in vivo toxicities;
- establishing mouse models that faithfully report the activation of (cancer cell-selective) anti-tumour pathways;
- synthesising and validating novel epi-drugs;
- verifying the concept of drug sensitisation by signalling crosstalk;
- establishing novel models to study epi-drugs in solid tumours
By dint of the multi-disciplinary nature of the consortium, an entire pipeline to accomplish these goals was established and in addition to the strong fundamental basis in basic research, the team's expertise included drug design and synthesis, whole-genome approaches and high-throughput screening, clinical interface, as well as the development and use of mouse models which accurately reproduce the human disease.
