Time to stratify? The retinoblastoma protein in castrate-resistant prostate cancer

It is generally held that the retinoblastoma (RB) tumor suppressor functions in multiple tissues to protect against tumor development. However, preclinical studies and analysis of tumor samples of early disease did not support an important role of RB loss in the origin of prostate cancer. By contrast, recent observations in the clinical setting and subsequent modeling of RB function indicate that the tumor suppressor has specialized roles in controlling androgen receptor expression in prostate cancer, and primarily functions to prevent progression to the castration-resistant stage of disease. Furthermore, preclinical models have now shown that loss of RB expression or functional activity decreases the effectiveness of hormone therapy, yet seems to increase sensitivity to a subset of chemotherapeutic agents. Here, the current state of knowledge regarding the implications of RB loss for prostate cancer progression will be reviewed, and potential opportunities for developing RB as a metric to predict therapeutic response will be considered.