Figure 3. RBM10 deficiency limits the therapeutic efficacy of EGFR TKIs.
(A and B) Waterfall plots representing immunodeficient mice bearing H3255 (A) or PC-9 (B) tumor xenografts expressing either shScr control or shRBM10. Mice were treated with 2 mg/kg (H3255) or 5 mg/kg (PC-9) osimertinib once daily over 14 days (n = 10 tumors per treatment cohort). Percentage changes in tumor volume compared with baseline volume (day 0) for individual tumor xenografts are shown. (C and D) H3255 and PC-9 tumor xenograft explants demonstrating the effect of RBM10 KD on PARP cleavage in mice treated with osimertinib or vehicle for 14 days. One tumor of representative size from each group was harvested 4 hours after the indicated treatments on day 15, and subsequent analyses of the indicated proteins was performed by Western blotting. (E–G) PC-9 cells expressing either shScr or shRBM10 in a validated orthotopic lung tumor model were treated with 5 mg/kg osimertinib once daily for 60 days. Representative bioluminescence images (E) and mean relative photon flux (F) are shown. *P < 0.05. (G) PFS comparing the PC-9 shScr control and PC-9 shRBM10 mice (P = 0.0002, Wilcoxon test).