Emerging Targets for Prostate Adenocarcinoma Therapy: How Molecular Biology May Drive Towards a More Tailored Approach?

Prostate adenocarcinoma is the most diagnosed male cancer in the Western world and the second leading cause of cancer-related mortality. Albeit most of the patients with prostate adenocarcinoma are currently treated by surgery and/or radiation therapy, more than 30-40% of affected subjects will eventually progress and develop advanced disease. To date, management decisions depend on the clinical stage of the patient and the histological diagnosis which unfortunately often lack to predict the real prognosis. Current therapies have shown to be insufficient, mainly in the metastatic disease. For clear-cut diagnosis and follow-up, we promptly need molecular markers also useful in predicting patient's outcome. Advances in cancer genomics have led to a plethora of biomarkers, which must now to be rigorously validated in the clinical setting. Recent insights on prostate adenocarcinoma biology which unveiled some of the biological mechanisms leading to this tumour, have managed in devising novel strategies for therapy. Immunotherapeutic agents, selective adrenal inhibitors, anti-angiogenic molecules, newly engineered androgen receptor inhibitors, compounds targeting the bone microenvironment are demonstrated to limit cancer growth by blocking specific signaling pathways. Such strategies can be complemented to existing therapeutic paradigm in improving beneficial outcome. Moreover, other emerging pharmacological compounds have shown encouraging results and several clinical trials are ongoing. This review summarizes the developing targeted therapies for prostate adenocarcinoma and discuss their potential benefit mainly in the castration-resistant forms.