A renaissance in targeting the PI3K/AKT/mTOR pathway.

The PI3K/AKT/mTOR pathway represents an excellent drug target, given its proven druggability and roles in cancer, immune regulation and genetic disorders. However, although some agents targeting this pathway have gained approval, drug development has faced challenges due to tolerability issues and resistance mechanisms, amongst other obstacles. New pharmacological approaches and improved biological and clinical understanding are now renewing interest and confidence in therapeutically modulating PI3K/AKT/mTOR signalling. This Perspective covers the challenges, lessons learned and new efforts in targeting this pathway.