Next-Generation Therapies in CRPC Take Aim at AR Resistance

Ariela Katz
Published: Wednesday, Apr 19, 2017
Robert Dreicer, MD, MS

Robert Dreicer, MD, MS

As a wealth of research has shown in the past several years, therapies that target the androgen receptor (AR) pathway in patients with castration-resistant prostate cancer (CRPC) encounter complex mechanisms of resistance including the likelihood that more than 1 such signaling network is active in each individual (Figure).

Figure. Androgen Receptor Targeting and Resistance in Prostate Cancer

Figure. Androgen Receptor Targeting and Resistance in Prostate Cancer

Dreicer explained that clinicians will start a patient on either AR inhibitor and, if the patient does not have a durable response, then they will usually switch to docetaxel followed by the other AR inhibitor option, despite the clinician’s doubts of efficacy.

Signals From AR-V7 Variants

AR-V7 splice variants have gained much attention in recent years. Immunohistochemistry staining has established their increased expression in patients with CRPC. It has been shown to regulate both AR-regulated genes and a unique set of genes independent from the AR, suggesting that it has an overlapping, yet distinct, role compared with full- length AR in prostate cancer cells.1
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