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Updated: Apr 20, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate
Roberta Ferraldeschi1, Daniel Nava Rodrigues1, Ruth Riisnaes1
1Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, Surrey, UK.
Background:
Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.
Objective:
To explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.
Design, Setting, And Participants:
We retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.
Outcome Measurements And Statistical Analysis:
The primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.
Results And Limitations:
A total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.
Conclusions:
Our results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.
Patient Summary:
PTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.
Insights
Loss of phosphatase and tensin homolog (PTEN) in prostate cancer patients treated with abiraterone acetate is linked to poorer survival outcomes. This finding highlights PTEN status as a crucial factor in predicting treatment response and prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Loss of the tumor suppressor PTEN is common in prostate cancer.
- PTEN loss can activate PI3K/AKT signaling, potentially leading to resistance to hormonal therapies.
Purpose of the Study:
- To investigate the antitumor activity of abiraterone acetate in castration-resistant prostate cancer (CRPC).
- To compare treatment outcomes in CRPC patients with and without PTEN protein loss.
Main Methods:
- Retrospective analysis of 144 patients treated with abiraterone post-docetaxel.
- PTEN immunohistochemical analysis of tumor tissue.
- Overall survival and duration of abiraterone treatment were primary endpoints, analyzed using Cox regression and log-rank tests.
Main Results:
- PTEN loss was observed in 40% of patients.
- Loss of PTEN expression correlated with significantly shorter median overall survival (14 vs. 21 months) and abiraterone treatment duration (24 vs. 28 weeks).
- PTEN protein loss, high LDH, and visceral metastases were independent prognostic factors.
Conclusions:
- Loss of PTEN expression is associated with worse survival and reduced efficacy of abiraterone treatment in prostate cancer.
- Further prospective studies are needed to validate these findings in larger patient cohorts.
