Among the molecular alterations observed in prostate cancer, PTEN loss represents a key event, functionally linked to aberrant activation of the PI3K/AKT/mTOR pathway. Loss of PTEN function contributes to disease progression, therapy resistance and poor prognosis. This review highlights the biological significance and the prognostic role of PTEN in prostate cancer, the biologically relevant crosstalk between the PI3K and androgen receptor pathways, and the implications of this interaction for tumour adaptation and treatment resistance. We also discuss current methodologies for PTEN assessment, including immunohistochemistry and genomic techniques, and provide an overview of clinical trials targeting the PI3K/AKT axis in prostate cancer. Understanding PTEN alterations is essential for improving prognostic stratification and guiding precision oncology approaches.
Critical reviews in oncology/hematology. 2026 Jul 24 [Epub ahead of print]
D Alaimo, F Di Costanzo, M Oltrecolli, C Oing, E Castro, P Rescigno
Northern Centre for Cancer Care, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Department of Internal Medicine and Medical Therapy, University of Pavia, 27100 Pavia, Italy; Department of Oncology, Comprehensive Cancer Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy., Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Medical Oncology, Università degli Studi di Napoli Federico II, Naples, Italy., Northern Centre for Cancer Care, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Department of Oncology & Hematology, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy., Northern Centre for Cancer Care, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Hospital Universitario 12 de Octubre, Madrid, Spain., Northern Centre for Cancer Care, Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address: .