What have shown studies conducted by Ferraldeschi et al. utilized IHC to study PTEN expression?
Studies conducted by Ferraldeschi et al. utilized IHC to study PTEN expression in a cohort of metastatic CRPC samples. They found that lack of PTEN expression correlated with both poor survival and decreased the time of response to abiraterone. The heterogeneity of PTEN expression has been well observed within prostate cancers. However, its comparison and the enrichment shown of PTEN aberrations in CRPC through use of sequencing and histological studies have suggested that PI3K-AKT hyperactivity also plays an important role in the development of prostate cancers. Haffner et al carried out a study where an autopsy was conducted on a patient who had died showing extensive PTEN mutation. The lethal clone was mapped to a minute focus of PTEN-IHC negative disease in the prostatectomy specimen, which further shows circumstantial evidence that aberrations in the PI3K-AKT pathway are associated with the clinically aggressive disease.
The presence of compounds that can be utilized to inhibit both PI3K kinases and its downstream targets such as AKTs and mammalian target of rapamycin (mTOR) has led to the possibility of alterations in the PI3K-AKT pathway as being a critical predictive biomarker. The combination of mTOR inhibitors and aromatase inhibitors have shown increased progression-free survival in hormone receptor-positive advanced breast cancer in postmenopausal women compared to monotherapy with aromatase inhibitors. Current responses of monotherapy in prostate cancers have so far yielded disappointing results (21). However, current trials using mTOR inhibitors in combination with androgen blockade are currently underway. As are trials using PI3K kinases inhibitors and AKT with AR-signalling inhibiting agents, while PTENs utility as a biomarker is currently under investigation in a phase ll trial of PI3K/mTOR and AKT inhibitors combined with abiraterone + prednisone versus abiraterone + prednisone alone. The potential of PTEN status as a predictive biomarker still warrants further investigation along with the development of a comprehensive PI3K-AKT pathway biomarker suite.