Androgen receptor targeting drugs in castration-resistant prostate cancer and mechanisms of resistance

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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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D J Crona1, M I Milowsky2,3, Y E Whang2,3

  • 1Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.

Clinical Pharmacology and Therapeutics
|September 3, 2015
PubMed

Insights

New therapies targeting androgen receptor (AR) signaling are crucial for castration-resistant prostate cancer (CRPC). Novel agents show promise in overcoming resistance mechanisms, potentially improving patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Urology

Background:

  • Reactivated androgen receptor (AR) signaling is a key driver of castration-resistant prostate cancer (CRPC).
  • Current AR-targeting drugs like abiraterone and enzalutamide improve survival but resistance eventually develops.
  • Mechanisms of resistance include AR splice variants (e.g., AR-V7), AR mutations (e.g., F876L, T877A), and alterations in androgen biosynthesis or glucocorticoid receptor.

Purpose of the Study:

  • To review emerging therapeutic strategies for overcoming resistance in CRPC.
  • To highlight novel agents and biomarkers that may improve treatment efficacy.
  • To discuss the role of AR signaling and its resistance mechanisms in CRPC progression.

Main Methods:

  • Review of current literature on CRPC treatment resistance.
  • Analysis of novel therapeutic agents targeting AR signaling pathways.
  • Evaluation of biomarkers, such as AR-V7, for patient stratification.

Main Results:

  • Novel agents like galeterone (AR protein degradation) and EPI-001 (AR splice variant inhibition) show potential against resistance mechanisms.
  • Galeterone is being evaluated in AR-V7 positive CRPC patients.
  • AR-V7 is identified as a promising biomarker for treatment selection.

Conclusions:

  • Emerging therapies targeting AR signaling offer new hope for CRPC patients.
  • Understanding and overcoming AR-mediated resistance is critical for improving survival.
  • Novel biomarkers like AR-V7 can guide personalized treatment strategies in CRPC.

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