GRB2 and cancer: Another preclinical study conducted by Chen et al. on lung cancer cell lines resistant to EGFR-TKIs demonstrated that lymecycline, a semisynthetic derivative of tetracycline, was able to reverse cancer cells’ resistance to icotinib, an EGFR-targeting TKI, by inhibiting EGFR phosphorylation and growth factor receptor-bound protein 2 (GRB2)-mediated AKT/ERK/STAT3 signaling pathways, resulting in a synergistic effect with these two drugs [95].