NRG1 and neoplasm: Decreased VEGF levels in trastuzumab-treated tumors did not change CD31 vessel density [17], indicating that many mechanisms contribute to resistance to trastuzumab, including support of tumor vasculature by tumor cells and upregulation of pro-angiogenic factor heregulin in order to compensate for decreased VEGF production caused by the presence of trastuzumab [18].