MEK or PI3K/mTOR inhibition resulted in antitumor effects for these gefitinib-resistance NSCLC models by blocking key intracellular pathways controlling cell proliferation and survival as demonstrated both in vitro and in vivo. Surprisingly, PI3K/mTOR inhibition by BEZ235 also suppressed lung tumor angiogenesis and targeted both MEK and PI3K/mTOR activation in lung tumors, resulting in substantial antiangiogenic effects, which may due to the significantly reduced expression of MMP-9 in tumors. The gene discussed is MMP9; the disease is non-small cell lung carcinoma.