Radiotherapy improves efficacy of the PARP inhibitor Niraparib in a preclinical model of triple negative breast cancer

PARP inhibitors (PARPi) are a class of cancer therapeutics that specifically target poly-ADP-ribose polymerase (PARP), a key protein involved in DNA repair pathways. In triple-negative breast cancer (TNBC) cells often harbour defects in the homologous recombination pathway, which plays a critical role in repairing DNA double-strand breaks. In the context of homologous recombination deficiency, PARPi indirectly increase the frequency of unrepaired double-strand breaks by affecting the base excision repair pathway. This effect is particularly relevant after DNA-damaging stresses, such as those induced by radiotherapy. The combination of PARPi with radiotherapy can exploit these DNA repair mechanism defects, leading to increased DNA damage, and ultimately cell death. This study presents data modelling the combination of radiotherapy with a PARPi in a preclinical model of TNBC.