Treatment-resistance to DNA damaging targeted therapies resulted in the emergence of new, therapy-specific clusters. a, Tumor growth for MDA-SC4s vehicle, PARPi-treated (talazoparib), and CHKi-treated (prexasertib) mice (n=3 mice per treatment). Tumors were collected when tumor volume doubled from onset of treatment. b, Pooled t-SNE plot of the MDA-SC4 vehicle, PARPi-relapsed and CHKi-relapsed cells in combination with all seven other CDXs (MDA-SC39s, MDA-SC68s, HCI-008s, MDA-SC16r, MDA-SC49r, MDA-SC55r and MDA-SC75r; n=2,000 cells each). Emergence of unique clusters were detected following relapse to PARPi or CHKi. t-SNE visualization of cell populations from MDA-SC4 vehicle, PARPi- and CHKi-relapsed tumors form three clusters. c, Percentage of cells from MDA-SC4 vehicle, PARPi-relapsed and CHKi-relapsed samples within the clusters. d, ITH score was higher in CHKi-relapsed (P=4.4e-65) or PARPi-relapsed (P=7.5e-132) samples compared to vehicle samples by two-sided Wilcoxon rank sum test (n=2,000 cells each). Center lines show the medians; box limits indicate the 25th and 75th percentiles; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles.