Fig. 6: NIF/PARPi combination induced synthetic lethality in PARPi-resistant PDXs.

A Circos plot showing genomic variations in PDX models. Color-coded chromosomes are arranged around the outside of the circle; CNA is shown in the inner ring (green, deletion; red, gain). Mutations and Genomic Instability index (GI index) are located inside the circus plot. B–E Effect of NIF and PAPRi treatment alone or in combination on the tumor growth of each PDX, compared with the vehicle-treated condition (CTRL). The gray area corresponds to the treatment period. Growth curves represent the mean ± SEM of tumor volume for n = 8 tumors per treatment group. F–I. Box plots represent bCSC frequency calculated using an extreme limiting dilution analysis (ELDA). The results are expressed as the estimated number of bCSCs for 100 tumor cells. n = 15 injections per PDX. J–M Detection of click-melphalan (Melphalan-C) or click-M2 (M2-C) residual DNA lesions after different time points of treatment in patient-derived organoids (PDXOs) (upper panel). Dot plots represent the percentage of fluorescent positive cells for Melphalan-C (in red) and M2-C (green) at different time points and for each PDXO. n = 4 independent experiments. In (F–I) box represents mean ± margin of error (95% Confidence Interval), and in (J–M), data are shown as mean ± SD. ns (not significant), *P < 0.05, **P < 0.01, and ***P < 0.001 according to two-way ANOVA followed by Bonferroni correction (B–E, G), one-sided Chi-squared test (F–I), and two-way ANOVA followed by sidak multiple range test of 3 independent experiments (J–M). Source data are provided as a Source Data file.