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. The gene discussed is TGFB2; the disease is non-small cell lung carcinoma.