Early experiments in lung adenocarcinoma A549 cells [111] showed that termination of p-EGFR signals by gefitinib resulted in phosphorylation and activation of the cell cycle regulator protein p53 (Box 1), followed by p53-dependent upregulation of PUMA, a pro-apoptotic, BCL2 homology 3 (BH3) domain-containing member of the BCL2 family [112], which activates rapid induction of the caspase-dependent intrinsic apoptosis pathway (reviewed in [113]) (Figure 3). Here, BCL2 is linked to lung adenocarcinoma.