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Aim and objectives
The main aim of this proposal is to exploit our extensive knowledge of the DDR to optimise and further personalise cancer therapies, while minimising side effects.
Three major, specific objectives based on this concept are envisaged:
- Systematic assessment of normal tissue consequences of PARP inhibitors using an arsenal of specific and high-throughput ('-omics') approaches on mouse models and clinical samples. These investigations will optimise and customise the use of drugs that target the DNA damage response.
- Design of novel types of ex vivo assays using viable tumour tissue, which identify the subpopulation of cancer patients eligible for application of PARP inhibitor protocols. We intend to develop a novel generation of rationale-based laboratory tests assessing response parameters of viable tumour tissue samples, built on existing knowledge of molecular mechanisms, which will enable diagnosis and treatment in a tailor-made fashion.
- To expand the powerful concept of synthetic lethality based on compromised DNA damage response of tumours as a basis for novel, highly selective cancer treatment modalities for subtypes of other tumours. This is carried out by exploring the realm of new possible synthetic lethal combinations of DDR defects by extensive systematic screenings in relevant model systems, such as S.cerevisiae, C. elegans and mammalian cell lines.