What are the main subgroups of the metastatic prostate cancer?
Metastatic prostate cancer can be subdivided into two subgroups: hormone-sensitive prostate cancer (HSPC). Which response to androgen ablation and castration-resistant prostate cancer (CRPC), which develops resistance to gonadal suppression. Bilateral orchiectomy currently represents the gold standard for metastatic HSPC although gonadal suppression is currently accomplished through the use of gonadotropin-releasing hormone agonists or antagonists with or without androgen receptor blockade. It is this approach that remains the go-to therapy for those with metastatic HSPC. Recent data from stage all trials have also suggested a substantial survival benefit in the treatment of patients with combination therapy of docetaxel and androgen deprivation in metastatic HSPC.
However, despite these treatment options, most individuals suffering from metastatic HSPC will eventually progress the CRPC, the lethal stage of the disease. For patients progressing to this stage there exists several therapies providing benefit through suppression of androgen signaling (abiraterone, enzalutamide), disruption of the cell cycle in replicating cells (cabazitaxel, docetaxel), targeting of bone metastasis (radium-223), or activation of antitumor immunologic response (sipuleucel-T) (6). Although the contribution of these various therapies has resulted in an overall median increase in survivability in patients with metastatic CRPC, their impact on survival has been modest at best, and they do not have an impact in all men. On top of this, there is a distinct lack of validated genomic markers allowing for better stratifying of patients for these therapies, the ideal approach would be to obtain a genetic profile of an individual’s cancer and utilise the therapies allowing for the best outcome.
The advances in and subsequent development of high-throughput sequencing technologies has resulted in the ability to comprehensively analyze genetic mutations and resultant changes in gene expression in a patient’s prostate cancer. Such analysis is routinely performed in institutions with the aim to uncover molecular features allowing for the prediction of response to therapeutics or guiding patient stratification for clinical trial selection. The use of precision medicine aims to provide the right therapeutics for the right patients and regarding prostate cancer aims to molecularly characterize a tumor and utilize drugs promoting tumor lethality based on these uncovered molecular features. However, the limitations of such an approach are that it requires the target to be truly biologically relevant and that there are drugs that can effectively target these molecular changes.