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General Introduction


The recent use of specific inhibitors to down-regulate particular DNA damage response pathways in cancer therapy is exemplified by the highly successful clinical trials with PARP1 inhibitors on BRCA1/2-deficient breast/ovarian tumours. This case illustrates the power of combined interference with different DNA damage response processes to combat cancer: Homologous recombination, which is selectively deficient in the tumour due to the BRCA defect, and base excision repair of single strand breaks, which is blocked by the administration of PARP inhibitors. The huge therapeutic potential of cancer treatment with the aid of selective DDR interference was recently recognised by Nature to belong to the 10 most important breakthroughs in the entire spectrum of sciences in 2009 and the most pertinent development in the wide field of Cancer Research (Highlight in Nature 462, p. 961, 2009). It is the treatment par example of tailor-made, very effective cancer therapy, with comparatively minimal side effects. In this regard, the selective action of PARP inhibition on BRCA1/2 deficient tumours appears to be a 'magic bullet' therapy for this type of cancer.