PIK3CA and cancer: PI3K/AKT is activated in cancer by several different mechanisms, including somatic activating mutations (e.g., PIK3CA and PIK3R1), the amplification of genes encoding key components (e.g., PIK3CA and AKT), and the amplification/overexpression of upstream receptor tyrosine kinase (e.g., insulin-like growth factor receptor 1, HER2) [89].