PARP inhibtors induced a senescence phenotype in non-small cell lung carcinoma cell lines

Several anti-cancer treatments have been shown to activate the DNA damage repair pathway but also, in some cases, to lead to therapy-induced senescence. Senescent cells can either exert pro-tumoral or anti-tumoral effects. However, it remains poorly characterized which treatments lead to a senescent state. Our findings identify Talazoparib, a PARP1 inhibitor, as the most potent inducer of senescence in non-small cell lung carcinoma cell lines among a variety of PARP1 inhibitors. In the absence of PARP1, no senescence phenotype was observed thus demonstrating that PARP1 is necessary for the induction of senescence in non-small cell lung carcinoma cells exposed to Talazoparib. This enzyme is also required to induce an increase in cell death with the addition of Navitoclax (ABT-263), a senolytic drug. As senescence has been shown to have several pro-tumoral effects, these results demonstrate the importance of determining which anti-cancer therapies induce a senescence phenotype as it could lead to treatment failure but also to design drug combinations targeting this pathway to further enhance anti-cancer treatment efficacy.