PIK3CA and colorectal neoplasm: AKT is known to phosphorylate and inhibit GSK3 leading to increased beta-catenin activity.34 More recent data has demonstrated that colorectal tumors that have high levels of beta-catenin are more resistant to PI3K/AKT inhibition.35 The exact mechanism of porcupine induction after pan-PI3K inhibition is currently unknown, and warrants further investigation.