PIK3CA and cancer: In retrospect, the limited pediatric preclinical activity is not surprising as experience for adult cancers has shown that genomic alterations leading to PI3K pathway activation are the primary predictors of clinical activity for pathway inhibitors, as illustrated by the approval of the PIK3CA inhibitor alpelisib for use in combination with fulvestrant for patients with advanced or metastatic breast cancer whose tumors having activating PIK3CA mutations (Narayan et al., 2021).