A renaissance in targeting the PI3K/AKT/mTOR pathway
Summary
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 modul
Content
# A renaissance in targeting the PI3K/AKT/mTOR pathway
*Published: 2026 Mar 30*
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.
DOI: 10.1038/s41573-026-01388-5