Figure 4 (IMAGE) Impact Journals LLC Caption Analysis of efficacy of targeting different DNA repair pathways on PALB2 mutated CAC cells. (A) Bar graphs showing the mean z-score and standard deviation of 3 individual siRNAs against core HR pathway genes. In each graph the left two bars show the viability z-score and right two bars the γH2Ax z-score in control condition (black) and with 500 nM ODM-207 (grey). (B) Distribution of the RNAi loss-of-function effects of the core HR genes divided according to the associated DNA repair pathway on untreated and BETi treated CAC cells. (C) ODM-207 and Olaparib exhibit a combinatorial additive effect on the PALB2 deficient cells. Dose-response matrix of percent of viability inhibition (left) and percent of cells with more than 5 nuclear γH2Ax foci (center) in response to increasing doses of ODM-207 (BETi) and Olaparib (PARPi). The combinatorial cytotoxicity was quantitatively analyzed by combination index (CI) combination index. With 1:4 molar ratio the CI50 of the drugs was 0.61, with 1:2 molar ratio 0.71, and with 1:1 molar ratio 0.89. (D) Representative 10× fluorescence microscopy images of the CAC cells stained for γH2AX (red) following 7d exposure to the combination of ODM-207 and Olaparib at 1:4 molar ratio. DNA staining shown in blue. Scale bars 100 μm. Credit Correspondence to - Juha K. Rantala - rantala@misvik.com Usage Restrictions Copyright: © 2021 Mäkelä et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. License Licensed content Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.