Prostate cancer is the second leading cause of cancer deaths in the USA. The challenge in managing castration-resistant prostate cancer (CRPC) stems not from the lack of therapeutic options but from the limited duration of clinical and survival benefit offered by treatments in this setting due to primary and acquired resistance. The remarkable molecular heterogeneity and tumor adaptability in advanced prostate cancer necessitate optimization of such treatment strategies. While the future of CRPC management will involve newer targeted therapies in deliberately biomarker-selected patients, interventions using current approaches may exhibit improved clinical benefit if employed in the context of optimal sequencing and combinations. This review outlines our current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance, highlighting targetable and reversible mechanisms of resistance.

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Published in Current Oncology Reports, v. 19, issue 2, article 13, p. 1-20.

© Springer Science+Business Media New York 2017

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This is a post-peer-review, pre-copyedit version of an article published in Current Oncology Reports. The final authenticated version is available online at: https://doi.org/10.1007/s11912-017-0568-7

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We acknowledge the support of this work through funding from the James F. Hardymon Endowment in Urologic Research at the University of Kentucky (NK), NIH grant K23CA197526 (CP); the National Center for Advancing Translational Sciences, UL1TR000117 (MN); and the Dean of the College of Medicine at the University of Kentucky.