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Aggressive variants of prostate cancer - Are we ready to apply specific treatment right now? Cancer Treat Rev. In most cases, prostate cancer essentially depends on androgen receptor signaling axis, even in castration-resistant setting, and hence may be targeted by second generation hormonal therapy. However, a subset of patients bears androgen-independent cancer biology with a short-term response to hormonal treatment, early and extensive visceral metastases, low PSA levels and poor outcomes. Identification and specific management of these rapidly fatal malignancies is of an unmet medical need since their classification and utilized therapeutic regimens vary significantly.