Fig. 6: Combined modality strategies and therapeutic windows for the combinational therapy of hyperthermia and WEE1 inhibition.

a Flow diagram of the sequential or concurrent combination modality strategies of hyperthermia (HT, 42 °C for 90 min) and WEE1 inhibitor (WEE1i, AZD1775). b, c Dose-response curves of the sequential or concurrent combined strategies of HT and WEE1i in OVCAR8, A2780, and ID8 cell lines. The ΔAUC% was calculated compared to WEE1i mono-therapy (n = 4 per group). d Flow diagram of the concurrent or various sequential combination strategies with HT and WEE1i. OVCAR8, A2780, and ID8 cells were treated with increasing doses of AZD1775 for 48 h in the presence (concurrent therapy) or absence (WEE1i mono-therapy) of HT incubation or cells were first treated with HT for 90 min, then returned to normothermia (37 °C). AZD1775 was administered at various normothermia recovery time points (0, 6, 12, 24, and 48 h) for 48 h. e, f Dose-response curves and ΔAUC% of various combined modality strategies are shown (n = 4 per group). Comparisons were performed by unpaired two-tailed Student’s t test in (c, f). Data are presented as mean ± SEM. ****p < 0.0001, ***p < 0.001, **p < 0.01, ns., not significant. All analytical data are derived from a minimum of three biologically independent experiments, with ‘n’ indicating the specific number of replicates. Source data are provided as a Source Data file.