AKT1 and colorectal carcinoma: Conversely, somatic mutations in PIK3CA can dampen the sensitivity of CRC cells to MEK inhibitors, while somatic mutations in PTEN might confer total resistance.88 Interestingly, a synergy in inhibiting both the PI3K/AKT and RAF/MEK/ERK pathways has been suggested to thwart the downstream mTOR pathway effectively58.