Alpelisib is the first oral inhibitor to selectively target the class-I phosphoinositide 3-kinase (PI3K) α-isoform and thereby block the (PI3K) pathway.6 In breast cancer, 35% of tumors harbor a PIK3CA mutation,7 and in specific subtypes (ie luminal A) this is up to almost 50%.8 Outside breast cancer, the PI3K pathway is frequently altered in endometrial (35–53%), cervical squamous cell (27%), bladder (20–23%), and colorectal cancer (15–21%). Here, PIK3CA is linked to colorectal cancer.