PIK3CA and breast carcinoma: This phenomenon is consistent with the well‐established feedback activation of PI3K/AKT as a major resistance mechanism in EGFR/mitogen‐activated protein kinase (MAPK)‐targeted therapies in solid tumors including CRC and breast cancer,[42] which is also associated with increased aggressiveness.[43, 44] Therefore, it might be interesting to evaluate if EGFR combination with HER‐2 or PI3K inhibitors offers more durable response in MSI KRAS/BRAF wildtype CRCs.