ABSTRACT Postzygotic mutations of the PIK3CA gene constitutively activate the PI3K/AKT/mTOR pathway in patients with PIK3CA ‐related overgrowth spectrum (PROS), causing congenital mosaic tissue overgrowth. We established primary fibroblast cells from a patient with a novel somatic frameshift mutation (c. 3190₃191insA, p. H1065fs) in PIK3CA, in which PI3K/AKT/mTOR signaling is activated compared to control fibroblasts. We assessed the therapeutic effects of three compounds (BYL719, ARQ092, and rapamycin) on the PI3K/AKT/mTOR signaling pathway and cell growth. Notably, BYL719 is more effective at inhibiting the overactivation of all key signaling molecules in the pathway at lower concentrations in patient‐derived fibroblasts, while showing no significant effect on control fibroblasts. The insertion frameshift mutation is not located within the five domains, but it is a gain‐of‐function PIK3CA mutation contributing to PROS development. The results further confirmed the obvious advantages of the compound in targeted therapy for PROS patients.
Xiong et al. (Sun,) studied this question.