Novel twists in hormone-mediated carcinogenesis

    1. Wayne D Tilley
    1. Dame Roma Mitchell Cancer Research Laboratories, School of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, Australia
    1. Correspondence should be addressed to W D Tilley; Email: wayne.tilley{at}

    This special issue of Endocrine-Related Cancer highlights key emerging concepts, novel twists and challenges in resistance to hormonal therapies for breast and prostate cancer. Emerging therapeutic strategies to overcome such resistance and advances in patient-derived xenografts to better model solid tumours are presented.

    The growth of prostate cancer is exquisitely dependent on androgens and the androgen receptor (AR). Thus, the primary treatment option for men with metastatic prostate cancer is androgen deprivation therapy (ADT), which suppresses androgen biosynthesis and/or binding of ligand to the AR. Although most men initially respond to ADT, their cancer inevitably returns in an incurable and lethal form termed castration-resistant prostate cancer (CRPC) (Scher et al. 2004). The advent of new-generation AR-targeting agents, such as the AR antagonist enzalutamide and the androgen biosynthesis inhibitor abiraterone, has improved survival outcomes for men with CRPC (Suzman & Antonarakis 2014). However, the overall survival benefits associated with these new treatment strategies are in the order of months (Recine & Sternberg 2015), highlighting the capacity for AR signalling to adapt to all forms of ADT and the intractable problems associated with therapies that only inhibit ligand activation of the AR ligand binding.

    Coutinho and coworkers specifically address key mechanisms underlying persistent AR signalling in CRPC and how this relates to resistance to AR target therapies (Coutinho et al. 2016). Although many such reviews are available in the literature, several novel features set this one apart from others. First, it comprehensively catalogues the spectrum of AR mutations and alternative splicing events identified in prostate cancer, including details on the frequency, function and tissue source of such alterations. Tabular summaries with this level of information are extremely useful and provide an important resource for researchers working in this field. Second, the authors integrate a review of oncogenic functions of AR …

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