Emerging Variants of Castration-Resistant Prostate Cancer

Abstract

Metastatic castration-resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR inhibition, in which the tumors become less dependent on the AR. In this review, we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications. Improvements in the understanding of the biologic mechanisms and molecular features underlying prostate cancer variants may help prognostication and facilitate the development of novel therapeutic approaches for subclasses of patient with CRPC.

Keywords: Aggressive variant; Androgen indifference; Androgen-independent prostate cancer; Castration-resistant prostate cancer; Neuroendocrine prostate cancer; Small-cell prostate cancer.

Conflict of interest statement

Compliance with Ethics Guidelines: Conflict of Interest: Panagiotis J. Vlachostergios declares that he has no conflict of interest. Loredana Puca declares that she has no conflict of interest.

Figures

Figure 1. Schematic illustrating the three main classes of treatment resistance to AR targeted therapies in prostate cancer