The Role of Androgen Receptor in Prostate Cancer

Chapter
Part of the Molecular Pathology Library book series (MPLB)

Abstract

Androgen receptor (AR) is a hormone-dependent transcription factor, involved in male dimorphism from embryogenesis to adulthood and highly expressed in the prostate. Upon activation by androgen binding, AR translocates to the nucleus, homodimerizes, and activates the transcription of specific androgen-responsive genes. This signaling pathway is subject to regulation by numerous factors such as AR transcriptional cofactors and co-regulators, posttranslational AR modifications, and crosstalk with other signaling pathways. Androgen signaling is required for the development and maintenance of normal prostate but also plays a key role in the initiation and progression of prostate cancer. Therefore, targeting the AR pathway is the first line of intervention for treating this disease. Unfortunately, most treated patients develop resistance through a variety of mechanisms that, for the most part, reactivate AR signaling. These mechanisms involve alterations of AR itself (amplification, mutation, alternative splicing, and posttranslational modifications), alterations of co-regulators, and/or activation through crosstalk with other signaling pathways. Although newer AR-directed strategies are being developed and tested in the clinical setting, the most effective approach in treating lethal prostate cancer remains an active area of research.

Keywords

Androgen receptor Androgen signaling Prostate transcription factor Castration-resistant prostate cancer Treatment resistance Pathway crosstalk 

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineWeill Cornell MedicineNew YorkUSA
  2. 2.Meyer Cancer Center, Weill Cornell MedicineNew YorkUSA
  3. 3.Englander Institute for Precision Medicine, New York-Presbyterian Hospital, Weill Cornell MedicineNew YorkUSA

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