p-AKT Protein Expression Predicts Response to AKT Inhibitor Combined with Docetaxel Therapy in Adenocarcinoma and Neuroendocrine Prostate Cancer

Abstract

Purpose: AKT inhibitors, such as capivasertib, have shown activity in specific patients with metastatic castration-resistant prostate cancer when combined with docetaxel although none have been approved. Although PTEN loss is often linked to AKT pathway activation and response to AKT inhibitors, clinical trials show no consistent association. This study uses patient-derived tumor models to identify biomarkers associated with an effective response to AKT inhibitor plus docetaxel. Experimental Design: Targeted DNA sequencing and im-munostaining for PTEN and phosphorylated AKT (p-AKT; Ser473) were assessed in 39 patient-derived xenografts (PDX) from patients with prostate cancer, including aden..