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Differential Functions of Stromal and Epithelial Androgen Receptor in Prostate Cancer Before and After Castration Resistant Stage

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Advances in Rapid Sex-Steroid Action

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Abstract

Androgen receptor (AR) has been the center of prostate cancer (PCa) therapy for decades, so androgen deprivation therapy (ADT) to suppress androgens binding to AR has become the major therapeutic option. However, the ADT is initially effective on blocking tumor growth, but eventually fails, leading to a stage of castration resistant prostate cancer and more advanced metastatic stage. The failure might be due to the nonspecific targeting of androgen/AR signaling without considering the tumor stage or cell types comprising the tumor microenvironment. The recent accumulating evidences indicate that the AR role is different in early (positive role) and advanced metastatic stage of PCa (suppressive role). In addition, AR was shown to act as a tumor promoter in luminal epithelial and stromal cells, but as a suppressor in basal and stem/progenitor/intermediate cells. Therefore, targeting androgen/AR signaling can suppress one type of tumor at a specific stage, but may lead to undesired more aggressive tumors. Accordingly, a combined therapy targeting both tumor stages and different cell types in the tumor microenvironment should be considered. Recently, several promising anti-androgen and anti-AR drugs have been developed and their efficiency is being tested. So, the combination therapy strategy to target metastatic tumors and other types of cells together with the new drugs targeting androgen/AR signaling might overcome the current failure of the ADT method and bring in more efficient therapy to battle PCa. This chapter describes the AR role in different tumor stages and cell types, and discusses the better therapeutic approaches with more effective outcome.

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Authors and Affiliations

  1. Department of Urology and Pathology, George Whipple Laboratory for Cancer Research, University of Rochester, Rochester, NY, USA

    S. Lee, K.- P. Lai, S. Yeh & C. Chang

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  1. S. Lee
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  2. K.- P. Lai
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  3. S. Yeh
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  4. C. Chang
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Correspondence to C. Chang .

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Editors and Affiliations

  1. University of Naples, Naples, 80138, Italy

    Gabriella Castoria

  2. Department of Pathology, II University of Naples, Naples, 80138, Italy

    Antimo Migliaccio

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Lee, S., Lai, K.P., Yeh, S., Chang, C. (2012). Differential Functions of Stromal and Epithelial Androgen Receptor in Prostate Cancer Before and After Castration Resistant Stage. In: Castoria, G., Migliaccio, A. (eds) Advances in Rapid Sex-Steroid Action. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1764-4_9

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