Strategies for overcoming EGFR mutant lung SqCCs with BMPR-II and p70S6K expression. (A) Combinational treatment with erlotinib plus mTOR inhibitor [100 nM rapamycin (Rap)] overcame the EGFR-TKI resistance in lung Beas/2b-19del cell line. (B) Treatment with BEZ235 or combinational treatment with erlotinib plus BMPR inhibitor (100 nM LDN193189, LDN) overcame the EGFR-TKI resistance in lung Beas/2b-19del cell line. Viability at 72 h was calculated as the ratio of drug-exposed cells to viable DMSO-treated cells. (C) Beas/2b-19del cell lines were treated with the indicated drug combinations for 24 h. Cell extracts were immunoblotted to detect the indicated proteins. (D) Balb/C nude mice were s.c. engrafted with Beas/2b-19del cells, and tumors were treated daily with vehicle control, erlotinib, erlotinib plus rapamycin, or BEZ235 at the indicated dose. The tumor volumes (y axis) are plotted over time (x axis).