Fig. 8: RhoA inhibition decreases brain metastatic outgrowth and osimertinib resistance in vivo.

A Kaplan–Meier analysis of brain metastasis incidence following intracardiac injection of R2 shCntrl or R2 shRHOA−2 cells into mice that were maintained on a Dox food diet and treated with either vehicle or osimertinib starting 12 days after injection. Brain metastasis incidence was detected by BLI. N = 10 animals for shCntrl/vehicle, N = 16 animals for shCntrl/osimertinib, N = 12 animals for shRHOA-2/vehicle, and N = 17 animals for shRHOA-2/osimertinib. P-values of shRHOA groups (compared to shCntrl+Vehicle) calculated by log-rank test. B Representative BLI images of animals with median cranial tumor burden from A for each group at the indicated timepoint. C Dot plot of ex vivo brain BLI from vehicle-treated R2 shCntrl and R2 shRHOA-2 mice harvested at Day 40. N = 9 animals for shCntrl, and N = 8 animals for shRHOA-2. Data is presented as mean values +/− SEM. P-value calculated by Mann–Whitney (two-sided). D Dot plot of ex vivo brain BLI from osimertinib-treated R2 shCntrl and R2 shRHOA−2 mice harvested at Day 47. N = 10 animals per group. Data is presented as mean values +/− SEM. P-value was calculated by Welch’s t-test (two-sided). For C and D, images of brains are from animals with median tumor BLI signal.