EREG and cancer: Moreover, high TAM-derived epiregulin (EREG) induces the formation of EGFR/ERBB2 heterodimers on cancer cells, induces AKT phosphorylation, and attenuates TKI-induced apoptosis, thereby reducing erlotinib therapeutic response in NSCLC patients.217 However, overexpression or knockdown of cancer cell-derived EREG does not affect the TKI sensitivity, indicating the importance of compensatory signaling pathways in TKI resistance.