Based on recent evidence showing that the tumor microenvironment can cause de novo resistance to PI3K signaling inhibitors by activating the HRG/ErbB3 axis31, it is critical that further scientific efforts include investigation of the role of the tumor microenvironment in HRG/ErbB3 mediated effects in cancers, including ovarian cancers. The gene discussed is HRG; the disease is ovarian carcinoma.