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Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects

Oncogene volume 34, pages 1745–1757 (2015)Cite this article

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Abstract

Androgen receptor (AR) signaling is a critical pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. However, over time, most tumors become resistant to ADT. The view of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years. Progress in understanding the disease biology and mechanisms of castration resistance led to significant advancements and to paradigm shift in the treatment. Accumulating evidence showed that prostate cancers develop adaptive mechanisms for maintaining AR signaling to allow for survival and further evolution. The aim of this review is to summarize molecular mechanisms of castration resistance and provide an update in the development of novel agents and strategies to more effectively target the AR signaling pathway.

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Authors and Affiliations

  1. Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK,

    R Ferraldeschi, J Welti, G Attard & J S de Bono

  2. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    J Luo

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  1. R Ferraldeschi
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Competing interests

Abiraterone acetate was developed at The Institute of Cancer Research (ICR), which therefore has a commercial interest in the development of this agent. JSdB received consulting fees from Ortho Biotech Oncology Research and Development (a unit of Cougar Biotechnology), consulting fees and travel support from Amgen, Astellas, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Dendreon, Enzon, Exelixis, Genentech, GlaxoSmithKline, Medivation, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis, Supergen and Takeda, and grant support from AstraZeneca and Genentech. GA received consulting fees and travel support from Janssen-Cilag, Veridex, Roche/Ventana and Millennium Pharmaceuticals, lecture fees from Janssen-Cilag, Ipsen, Takeda and Sanofi-Aventis and grant support from AstraZeneca and Genentech. GA is on the ICR rewards to inventors list of abiraterone acetate.

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Ferraldeschi, R., Welti, J., Luo, J. et al. Targeting the androgen receptor pathway in castration-resistant prostate cancer: progresses and prospects. Oncogene 34, 1745–1757 (2015). https://doi.org/10.1038/onc.2014.115

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