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Mechanisms of Therapeutic Resistance in Prostate Cancer

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
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Abstract

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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Abbreviations

ADT:

Androgen deprivation therapy

CRPC:

Castration-resistant prostate cancer

EMT:

Epithelial-mesenchymal transition

MET:

Mesenchymal-epithelial transition

ECM:

Extracellular matrix

TGF-β:

Transforming growth factor β

LBD:

Ligand binding domain

AR:

Androgen Receptor

PTEN:

Phosphatase and tensin homolog deleted on chromosome ten

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Acknowledgements

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.

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Correspondence to Natasha Kyprianou.

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Mary Nakazawa, Channing Paller, and Natasha Kyprianou declare that they have no conflict of interest.

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This article is part of the Topical Collection on Genitourinary Cancers

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Nakazawa, M., Paller, C. & Kyprianou, N. Mechanisms of Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep 19, 13 (2017). https://doi.org/10.1007/s11912-017-0568-7

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