Neither second nor third generation mTOR inhibitors have been described for use in APDS, and although greater efficacy in killing cancer cells may be preferable in oncology trials, APDS is likely to require more subtle degrees of regulation of the mTOR pathway, specifically downstream of PI3Kδ, with over inhibition of the PI3K-Akt-mTOR pathway in general potentially increasing toxicity, particularly in long-term use. The gene discussed is PIK3CA; the disease is cancer.