Loss of PTEN protein function has negative effects in prostate cancer

The authors aimed to determine whether abiraterone acetate (Zytiga) can be used to stop tumor activity in castration-resistant prostate cancer in patients with and without PTEN protein function.

PTEN is a protein that controls cell processes like survival, replication and movement within the body. It has recently been identified as a potential biomarker (an indicator of disease state or condition) used in prostate cancer, where loss of PTEN can suggest a poor prognosis (the likely outcome) following treatment.

Hormone-sensitive prostate cancer is cancer that can still be treated effectively with hormone therapy – treatment that targets the hormones involved in prostate cancer like testosterone. Castrate-resistant prostate cancer is resistant to hormone therapy and can no longer be effectively treated with it. Loss of PTEN is suggested to be associated with progression of cancer from hormone-sensitive to castration-resistant. 

The aim of this article was to determine whether PTEN had any effect on outcome in castration-resistant prostate cancer.

A total of 144 patients were used in this study who had been treated with abiraterone (Zytiga) and prednisolone following docetaxel (Taxotere) treatment for metastatic prostate cancer (cancer that has spread beyond the prostate). They had an average follow-up time of 4.7 years. PTEN decreased in 38% of the primary tumor samples (from the original tumor site) and in 50% of the metastatic (cancer has spread) castration-resistant cancer camples. This difference was not deemed to be significant. Overall 40% of patients experienced PTEN loss.

Both hormone-sensitive prostate cancer samples and castrate-resistant prostate cancer samples were available from 41 patients and were tested to determine if PTEN loss changed with disease progression. From this, 44% of hormone-sensitive patients experienced PTEN loss compared to 57% of castrate-resistant patients. Using advanced analysis, loss of PTEN function was confirmed as an independent predictor for overall survival (time taken from patient diagnosis until death).

Prostate specific antigen (PSA – protein found in the blood that is elevated when prostate cancer is present) was measured in both PTEN positive (increased PTEN activity; 97 patients) and negative (low amounts of or no PTEN activity; 57 patients) patients. 32% of PTEN negative patients noticed a PSA decrease of more than 50% compared to 43% of PTEN positive patients. 43% of PTEN negative patients noticed a PSA decrease of more than 30% compared to 55% of PTEN positive patients.

Overall abiraterone treatment time was shorter in PTEN negative patients (24 weeks) compared to PTEN positive patients (28 weeks). Overall survival in PTEN negative patients was 14 months compared to PTEN positive patients who had an overall survival of 21 months.

The authors suggested that loss of PTEN is associated with shorter treatment time and worse overall survival.

This study lacked information of comorbidities (one or more disease present in conjunction with prostate cancer) and tumor data so results need to be further verified.

If you would like further information on abiraterone and the effect of the drug on survival rates in castration-resistant prostate cancer please consult your doctor.