First, HER4 has been shown in other tumor cells to activate PI3K and the MAPK cascade [6,12,69,100,101,102] and, in osteosarcoma cells [100], neuroblastomas [103], gliomas [16], or gastric cancer cells [12], to promote growth and/or development of metastases by a HER4-mediated PI3K activation mechanism. Here, ERBB4 is linked to osteosarcoma.