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  • Review Article
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Evolution of androgen receptor targeted therapy for advanced prostate cancer

Nature Reviews Clinical Oncology volume 11, pages 365–376 (2014)Cite this article

Subjects

Key Points

  • The discovery of androgen dependence in prostate cancer in 1941 by Huggins and colleagues still remains the backbone for the treatment of advance-staged prostate cancer

  • Over the past decade, the better understanding of the mechanisms driving resistance to castration has led to development of abiraterone acetate and enzalutamide, two next-generation androgen receptor (AR) targeting agents

  • Several challenges remain including resistance to continued blocking of the AR axis, cross-resistance between agents, ideal sequence of administration, combination strategies, and coordination with other treatments

  • Molecular characterization of patients, through next-generation sequencing or transcriptome analysis, will help to dissect mechanisms of resistance and to identify biomarkers allowing the selection of patients for specific treatment

  • The improved understanding of intra-patient molecular heterogeneity and of the multiple, redundant and compensatory signalling networks in cancers supports a role for rational combinatorial, targeted therapeutic approaches

Abstract

The discovery of androgen dependence in prostate cancer in 1941 by Huggins and colleagues has remained the backbone for the treatment of this disease. However, although many patients initially respond to androgen depletion therapy, they almost invariably relapse and develop resistance with transition of the disease to a castration-resistant state. Over the past decade, the better understanding of the mechanisms that drive resistance to castration has led to the development of next-generation androgen receptor targeting agents such as abiraterone acetate and enzalutamide. This Review aims to revisit the discovery and evolution of androgen receptor targeting therapeutics for the treatment of advanced-stage prostate cancer over the years and to discuss the upcoming future and challenges in the treatment of this common cancer.

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Figure 1
Figure 2: AR targeting treatment strategies in CRPC.

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Authors and Affiliations

  1. Prostate Targeted Therapy Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, 15 Cotswold Road, Sutton, London, SM2 5NG, UK

    Yien Ning Sophia Wong

  2. Division of Cancer Therapeutics, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, 15 Cotswold Road, Sutton, London, SM2 5NG, UK

    Roberta Ferraldeschi & Johann de Bono

  3. Division of Clinical Studies, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, 15 Cotswold Road, Sutton, London, SM2 5NG, UK

    Gerhardt Attard

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  1. Yien Ning Sophia Wong
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  2. Roberta Ferraldeschi
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  3. Gerhardt Attard
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  4. Johann de Bono
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Contributions

Y.N.S.W. researched data for the article. Y.N.S.W. and R.F. made a substantial contribution to discussion of the content. Y.N.S.W., R.F. and J.d.B. wrote the article and all authors reviewed and edited the article prior to submission.

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Correspondence to Johann de Bono.

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Competing interests

All authors are employees of The Institute of Cancer Research, which has a commercial interest in abiraterone acetate. J.d.B. has served as a paid consultant for Astellas Pharma Inc., Janssen Biotech, Medivation and Sanofi.

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Wong, Y., Ferraldeschi, R., Attard, G. et al. Evolution of androgen receptor targeted therapy for advanced prostate cancer. Nat Rev Clin Oncol 11, 365–376 (2014). https://doi.org/10.1038/nrclinonc.2014.72

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