Fig. 4: Insight into the role of DNA damage response pathway on PARPi activity. | Cell Death Discovery

Fig. 4: Insight into the role of DNA damage response pathway on PARPi activity.

From: Increased efficacy of PARP inhibitors against cisplatin-sensitive and -resistant ovarian cancer cells mediated via ATR and ATM inhibition

Fig. 4

A Scheme for the investigated protein kinases that mediate cell cycle arrests and selective inhibitors of the indicated kinases used in this study. B Heatmap of combinational treatments using selective kinase inhibitors against either ATR, CHK1, WEE1 or ATM and niraparib, olaparib or rucaparib in the respective cell lines. The indicated data represent means of the log2 of the ratio of the IC50-values resulting from solo treatment and the IC50-values resulting from the respective combinational treatment (n = 3). C,D Cell cycle analysis upon treatment with the indicated PARPi alone, elimusertib (ATRi) or AZD1390 (ATMi) alone or the combination of the respective PARPi and ATRi or ATMi. Mean ± SD (n = 3) for the respective phase of the cell cycle. For statistical analysis One-way ANOVA following Dunnett’s test was performed for each phase and cell line, *P < 0.05, **P < 0.01; ***P < 0.001; ****P < 0.0001.

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