PARP-1 inhibitors:genetically specific compounds for therapy of BRCA1/2 defected cancers

Project leader: Ivana Fridrichová
Project duration: 2010 - 2012

Poly(ADP-ribose) polymerase-1 (PARP-1) represents an important novel target in cancer therapy. Recent evidence suggests that PARP-1 inhibitors could be used not only as chemo/radiotherapy sensitizers, but as single agents to selectively kill cancers defective in DNA repair, specifically BRCA1/2 associated breast cancers. Besides conceptual advance in therapy that PARP-1 inhibitors may represent, there are also issues that require investigation. This project will answer the question how specific the PARP-1 inhibitors are and if new and more specific PARP-1 inhibitors could be developed and identified. It will also answer whether inhibitors that target only PARP-1 allow greater BRCA1/2 selectivity. Additionally, the role of the kinases proposed to be involved in PARP-1 inhibition will be studied to find out if their inhibition may further sensitize BRCA1/2-deficient cells to PARP-1 inhibitors and thus prevent or overcome PARP-1 resistance.

Publications