AKT1 Q79K

Allelic imbalance at the AKT1 locus and clonal dominance of the AKT1 mutation were associated with progression free survival (PFS) in plasmaMATCH Cohorts C (capivasertib plus fulvestrant) and D (capivasertib alone) combined. Breast cancers with mutations in AKT1 frequently have allelic imbalance favouring the mutation, resulting in increased expression of mutant transcript. Allelic imbalance of AKT1, and/or clonally dominant AKT1 mutations, were prognostic for significantly greater PFS of patients treated with capivasertib.

Higher frequencies of AKT1 mutation were observed in several common cancers, including cervical, breast, osteosarcoma, brain, head and neck and colorectal in our study . AKT1 E17K was more commonly found in breast, brain and cervical cancer . Given the fact that III/IV patients are more common in AKT1 mutated group, it coincides with AKT inhibitors therapeutic prospects in a variety of advanced malignant tumors .

These data suggest that the different AKT paralogs have distinct roles in melanoma brain metastasis and that AKT and FAK may be promising therapeutic targets. Implications: This study suggests that AKT1E17K promotes melanoma brain metastasis through activation of focal adhesion kinase and provides a rationale for the therapeutic targeting of AKT and/or FAK to reduce melanoma metastasis.