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AR function in promoting metastatic prostate cancer

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Abstract

Prostate cancer (PCa) remains a leading cause of cancer-related death in the USA. While localized lesions are effectively treated through radical prostatectomy and/or radiation therapy, treatment for metastatic disease leverages the addiction of these tumors on the androgen receptor (AR) signaling axis for growth and disease progression. Though initially effective, tumors resistant to AR-directed therapeutics ultimately arise (a stage of the disease known as castration-resistant prostate cancer) and are responsible for PCa-specific mortality. Importantly, an abundance of clinical and preclinical evidence strongly implicates AR signaling cascades in the development of metastatic disease in both early and late stages, and thus a concerted effort has been made to delineate the AR-specific programs that facilitate progression to metastatic PCa. A multitude of downstream AR targets as well as critical AR cofactors have been identified which impinge upon both the AR pathway as well as associated metastatic phenotypes. This review will highlight the functional significance of these pathways to disseminated disease and define the molecular underpinnings behind these unique, AR-driven, metastatic signatures.

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Acknowledgments

We thank the Knudsen Lab for insightful discussions; Dr. T. Mankanme, M. Urban, and C. McNair critical reading of the manuscript; W.K. Kelly for expert assistance and feedback on clinical topics; and E. Schade for expert graphical and technical support.

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Authors and Affiliations

  1. Department of Cancer Biology, Thomas Jefferson University, 233 10th St., BLSB 1008, Philadelphia, PA, 19107, USA

    Michael A. Augello, Robert B. Den & Karen E. Knudsen

  2. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Michael A. Augello, Robert B. Den & Karen E. Knudsen

  3. Department of Urology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Karen E. Knudsen

  4. Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Robert B. Den & Karen E. Knudsen

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  1. Michael A. Augello
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Correspondence to Karen E. Knudsen.

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Augello, M.A., Den, R.B. & Knudsen, K.E. AR function in promoting metastatic prostate cancer. Cancer Metastasis Rev 33, 399–411 (2014). https://doi.org/10.1007/s10555-013-9471-3

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