Here, our studies suggest that specifically TGFβ2 signaling activation is autocrine in nature, and mimics a “tumor suppressor” effect in short-term perspective to suppress tumor cell metabolism, proliferation, and motility in the early cellular adaptive drug escape against erlotinib, resulting in a long term overall tumor survival promotion that would ascertain the ultimate persistence, proliferative resistance and survival of the NSCLC cells throughout the therapeutic stress. This evidence concerns the gene TGFB2 and neoplasm.