In a phase 2 clinical trial, perifosine failed to show single-agent activity in R/M-HNSCC patients, hindering further exploration of perifosine as monotherapy in this disease.492 The results of two ongoing phase 2 clinical trials will help us better understand how AKT inhibitors act in HNC patients (NCT01306045 and NCT05172258). Here, AKT1 is linked to head and neck squamous cell carcinoma.