Kurzfassung

To gain insight into the consequences of genomic alterations associated with defective HRR, we will perform comprehensive analyses of DSB repair upon treatment with different PARP inhibitors
(olaparib, niraparib, rucaparib, talazoparib) as well as genotoxic agents (trabectedin, cisplatin, etoposide, and combinations thereof) using patient-derived tumoroids provided by WP3. DNA damage
will be investigated by γH2AX staining, comet assays, and immunofluorescence detection of RAD51, RPA, and 53BP1....To gain insight into the consequences of genomic alterations associated with defective HRR, we will perform comprehensive analyses of DSB repair upon treatment with different PARP inhibitors
(olaparib, niraparib, rucaparib, talazoparib) as well as genotoxic agents (trabectedin, cisplatin, etoposide, and combinations thereof) using patient-derived tumoroids provided by WP3. DNA damage
will be investigated by γH2AX staining, comet assays, and immunofluorescence detection of RAD51, RPA, and 53BP1. To functionally explore DSB repair and pathway choice, we will perform in vivo DNA damage reporter assays covering HRR and classical/alternative non-homologous end joining. To elucidate the effects of PARP inhibitor-mediated sensitization to genotoxic agents, we will analyze suppression of PARP enzymatic activity versus PARP trapping using various concentrations of PARP inhibitors with different modes of action.
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