There are potentially multiple mechanisms for PI-3 kinase constitutive activation in colon cancer, for example, direct PI-3-K activation through PIK3CA mutation, PTEN loss, activation of AKT itself through activating mutations in its PH domain, receptor tyrosine kinases such as ERBB3 activation as well as KRAS (which is mutated in up to 45% of colorectal cancers) and which is upstream of both the PI-3 kinase and Map kinase pathways [84]. Here, PIK3CA is linked to colorectal cancer.