PIK3CA and cancer: Nevertheless, it should be noted that the PyMT viral oncoprotein promotes cancer by constitutive activation of the same pathways (SRC, RAS, PI3K) that are hyperactivated by breast cancer-relevant oncogenes such as receptor tyrosine kinases; thus, transformation by PyMT is strictly dependent on activation of PI3K77,121, which is in tune with the fact that PIK3CA mutations are the most frequent oncogenic mutations in human luminal breast cancer.