This mutational hotspot hyperactivates USP8, rescuing epidermal growth factor receptor (EGFR) from lysosomal degradation and ensuring its sustained signaling in Cushing's disease.
EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease.
This review presents new developments in the study of the genetics of CD and focuses on the USP8-EGFR system as trigger and target of corticotroph tumorigenesis.