The other type of mechanisms is compensatory activation of downstream or parallel signaling pathways (off-target), such as RAS-RAF-MEK-ERK, PI3K-PTEN-AKT-mTOR, IGF1R pathway, NF-κB pathway et al., which were common in both lung and breast cancer with acquired resistance to respective targeted therapy (1–4) and could be overcome by combination therapies. Here, NFKB1 is linked to breast carcinoma.