,15 Mutations and aberrations in expression of PTEN, PIK3CA, PIK3CB, PIK3C2A/G, PIK3R1/4, AKT2, and upstream receptor tyrosine kinases responsible for pathway activation have been reported in canine OS and are associated with poorer prognosis.16, 17, 18, 19 We have previously reviewed the PI3K-AKT-mTOR signaling cascade and its involvement in canine cancers, including OS.20 The gene discussed is PIK3CA; the disease is cancer.