Furthermore, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is downstream of PDGFR, EGFR and c-Met and has been shown to be hyperactive in chordomas [43], suggesting that this pathway may be a unifying mechanism through which abnormal signaling by a variety of different RTKs underlies the pathophysiology of chordoma. This evidence concerns the gene MET and chordoma.