Fig. 6: Combined treatment with a PIMi overcomes resistance to ipatasertib in vivo in ipatasertib-resistant models established either in vitro or in vivo.

a Tumor xenografts derived from LNCaP Par X1.6 or G-R3 X1.2 cells were established by subcutaneous injection into male NOD scid gamma (NSG) mice supplemented with testosterone. Mice were treated with indicated inhibitors and tumor volume was monitored over time. Fitted tumor growth curves from 9 mice per group are displayed. b Schematic depiction of the establishment of ipatasertib resistance in vivo. c Representative AKTi dose response curves from a 4-day viability assay with indicated cell lines. R0068 X1.2 cells (established in vivo) display similar AKTi resistance to that of G-R cells (established in vitro). Error bars represent SEM; n = 4 replicates. d (left) Response of Par X1.6 cells plated in DMSO-control medium or of G-R3 or R0068 X1.2 cells plated in ipatasertib-containing medium to the PIMi GDC-0339 was assessed using a 4-day viability assay. (right) As in (left) except all cells were plated in DMSO-control medium (Dose response curves for par X1.6 in left and right panels are identical). Error bars represent SEM; n = 4 replicates. e As in a except fitted tumor growth curves from mice bearing R0068 X1.2 xenografts (9 mice per group) are displayed. See also Supplementary Figs. 11–13. Source data are provided as a Source Data file.