AR-V7 and prostate cancer: The watershed for treatment selection?

• Prostate cancer is an androgen-dependent tumor, relying on the androgen receptor (AR).
• Translational research focuses on the identification of biomarkers predictive of treatment response.
• Recent advances highlighted the role of androgen receptor splice variants (AR-Vs), mainly AR-V7, as potential prognostic and predictive biomarkers.
• ARv-V7 seems to be a prognostic marker of aggressive cancer behavior, being associated with shorter survival in CRPC patients.
• AR-V7 seems to be involved in limiting the efficacy of androgen deprivation therapies, in mediating resistance to enzalutamide and abiraterone, and in influencing the prostate cancer sensibility to anti-microtubules chemotherapeutics.

The androgen receptor (AR) plays a key role in progression to metastatic castration-resistant prostate cancer (mCRPC). Despite the recent progress in targeting persistent AR activity with the next-generation hormonal therapies (abiraterone acetate and enzalutamide), resistance to these agents limits therapeutic efficacy for many patients. Several explanations for response and/or resistance to abiraterone acetate and enzalutamide are emerging, but growing interest is focusing on importance of AR splice variants (AR-Vs) and in particular of AR-V7. Increasing evidences highlight the concept that variant expression could be used as a potential predictive biomarker and a therapeutic target in advanced prostate cancer. Therefore, understanding the mechanisms of treatment resistance or sensitivity can help to achieve a more effective management of mCRPC, increasing clinical outcomes and representing a promising and engaging area of prostate cancer research.