The PI3K–AKT and MAPK–ERK pathways are important oncogenic cascades and play a critical role in cancer development and progression, but other oncogenic pathways, such as WNT signaling in colorectal cancer, breast cancer, and hepatocellular cancer, may be intrinsically activated or induced in response to inhibition of the PI3K–AKT and MAPK–ERK pathways. This evidence concerns the gene PIK3CA and colorectal cancer.