Tumor microenvironment-derived neuregulin 1 (NRG1), identified in cancer-associated fibroblast (CAF) supernatant, was shown to induce resistance in tumor cells through activation of human epidermal growth factor receptor-3 (HER3) and the subsequent downstream signaling molecules such as MAPK to promote cell proliferation and survival[104]. This evidence concerns the gene ERBB3 and neoplasm.