Upregulation of TAM-derived EREG may attribute to the activation of the JNK pathway by IL-1β in the TME.218 In erlotinib-resistant HNSCC, EREG/EGFR was found to upregulate the c-myc expression to stimulate cell proliferation.219 Furthermore, M2 TAMs can release HGF to bind to MET receptors in HCC tumor cells and induce sorafenib resistance. This evidence concerns the gene EREG and hepatocellular carcinoma.