EGFR and neoplasm: Here, we reviewed the molecular mechanisms of tumor drug resistance induced by EGFR, PI3K/Akt, Ras/MAPK, Wnt/β-catenin, Notch, Transforming growth factor-beta (TGF-β), and combinations of these signaling pathway inhibitors derivatives from natural products to overcome tumor resistance, provide new ideas and strategies for the rational clinical selection of antitumor drugs, and therefore improve patient quality of life and survival.