Multifaceted and personalized therapy of advanced prostate cancer

A number of molecular and genomic biomarkers that possess the ability to guide treatment or 'actionable targets' are being reported in metastatic prostate cancer. In addition, pathways of resistance to existing therapies and novel agents to overcome them are currently under active investigation. The next wave of investigations is focused on personalized therapy of prostate cancer. The focus of this review article is to provide an update on clinical development in advanced prostate cancer and to highlight the ongoing investigations of biomarker discovery, and ways of overcoming therapeutic resistance. The next generation of clinical trials developing novel targets and compounds promises to be in populations enriched with specific marker expression.

The breakthrough report, of the ability of the androgen receptor variant 7 mutation, detected in circulating tumor cells, to predict the lack of response to abiraterone or enzalutamide, and the remarkable responses of poly adenosine diphosphate ribose polymerase inhibitors in prostate cancer with DNA repair mutations have elevated hopes of a bright future in the biomarker-driven therapeutic arena. Novel targets such as bromodomain extra terminal-1 and phosphatidylinositol 3-kinase hold promise for the possibility of overcoming resistance. Novel hormone agents are also under active study.

As the clinical application of the multifaceted therapies narrows down to enriched patient populations selected by genomic testing, the therapeutic efficiency will escalate considerably. Novel targets, resistance mechanisms and relevant agents are being avidly tested, and the dream of personalized medicine is emerging into reality.