Mutations in the PI3K/AKT pathway, and low expression of PTEN and TP53 levels are also predictive of poor anti-EGFR efficacy.128–130 PI3K inhibitors and mTOR inhibitors are the two main targeted therapies directed against the PI3K/AKT pathway that have been used in renal cell carcinoma or in breast cancer, yet their use in CRC has not been well established, requiring further evaluation in clinical trials.131–134. Here, AKT1 is linked to hereditary clear cell renal cell carcinoma.