PIK3CA and colorectal carcinoma: However, the effect of PIK3CA mutations and loss of PTEN on anti-EGFR therapy seems relatively weak and alterations in the PI3K pathway often co-occur with other important driver mutations like KRAS and BRAF, indicating that the PI3K pathway plays a less critical role compared to the MAPK pathway in unresponsiveness to EGFR inhibition in CRC and maybe even in CRC in general [13, 51].