Fig. 5: Sequential ATR and PARP inhibitor treatment is effective in PDAC cell lines.

a Immunoblot from patient-derived cell lines probed for endogenous expression of DNA damage response markers. Cell lines are grouped according to DNA damage response (DDR) proficiency. Mutational variants (*), promoter hypermethylation (M) and amplification (A) of relevant genes for individual cell lines are indicated. b Immunoblot from patient-derived cell lines probed for replication stress response markers. Cell lines are grouped according to DNA damage response (DDR) proficiency and replication stress (RS) score (High or Low). Mutational variants (*), promoter hypermethylation (M) and amplification a of relevant genes for individual cell lines are indicated. c ZIP synergy score analysis for patient-derived cell lines after sequential treatment with ceralasertib and olaparib in a 5 × 5 matrix of dose combinations (Ten-fold dilutions, 0-10 μM). Results are grouped by DNA damage response proficiency and replication stress score (high, H; or low, L), and were analysed by 2-way ANOVA with Sidak’s multiple comparison test (*p < 0.05). d Graphical representation of clonogenicity assay results from sequential ceralasertib and olaparib-treated patient-derived cell lines. Results were analysed by nonlinear regression relative to the surviving fraction of the vehicle for pretreated (red symbol) or non-pretreated (clear symbol) conditions. Graphs are representative of 2 independent experiments and p values for significantly different curves are indicated.