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Oncogene. 2014 Oct 23;33(43):5053-64. doi: 10.1038/onc.2013.497. Epub 2013 Nov 25.

Metastatic castration-resistant prostate cancer: new therapies, novel combination strategies and implications for immunotherapy.

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Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.


For the past decade, docetaxel has remained the global standard of care for frontline treatment of metastatic castration-resistant prostate cancer (mCRPC). Until recently, there were limited options for patients with mCRPC following docetaxel failure or resistance, but now the approved treatment choices for these patients have expanded to include abiraterone acetate, cabazitaxel and enzalutamide. Additionally, the radioactive therapeutic agent radium-223 dichloride has been recently approved in patients with CRPC with bone metastases. Although each of these agents has been shown to convey significant survival benefit as a monotherapy, preclinical findings suggest that combining such innovative strategies with traditional treatments may achieve additive or synergistic effects, further augmenting patient benefit. This review will discuss the transformation of the post-docetaxel space in mCRPC, highlighting the spectrum of newly approved agents in this setting in the USA and the European Union, as well as summarizing treatments with non-chemotherapeutic mechanisms of action that have demonstrated promising results in recent phase 3 trials. Lastly, this review will address the potential of combinatorial regimens in mCRPC, including the pairing of novel immunotherapeutic approaches with chemotherapy, radiotherapy or androgen ablation.

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