Lessons from the Oncology Clinic: Repurposing PI3K Pathway Inhibitors for the Treatment of PTEN Hamartoma Tumor Syndrome

The underlying genetic abnormalities that cause the phenotypic variation seen in patients with PTEN hamartoma tumor syndrome (PHTS) are poorly understood. In this issue, Castillo and colleagues report that the somatic loss of PTEN through copy-neutral loss of heterozygosity and the resulting uniparental disomy in endothelial cells lead to vascular malformations in PHTS, which respond to PI3K/AKT/mTOR pathway inhibitors. See related article by Castillo et al., p. 1350 .