PIK3CA and carcinoma: To identify the potential escape pathways, we examined the impact of EGFR inhibition on the activity of two downstream pathways - PI3K/AKT and RAS/RAF/ERK (which were reported to be both inactivated in the gefitinib-sensitive carcinoma cell line A431 [21]), using the STS cell lines with wild-type EGFR TK, KRAS and BRAF genes (778, 449B and HT1080), so as to rule out any interference from gene mutation and using EGF to maximize downstream expression (Figure 2B and 2C, Supplementary Figure S2A).