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The Role of RB in Prostate Cancer Progression

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Prostate Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1210))

Abstract

The RB tumor suppressor is one of the most commonly deleted/mutated genes in human cancers. In prostate cancer specifically, mutation of RB is most frequently observed in aggressive, metastatic disease. As one of the earliest tumor suppressors to be identified, the molecular functions of RB that are lost in tumor development have been studied for decades. Earlier work focused on the canonical RB pathway connecting mitogenic signaling to the cell cycle via Cyclin/CDK inactivation of RB, thereby releasing the E2F transcription factors. More in-depth analysis revealed that RB-E2F complexes regulate cellular processes beyond proliferation. Most recently, “non-canonical” roles for RB function have been expanded beyond its E2F interactions, which may play a particular role in advanced prostate cancer. For example, in mouse models of prostate cancer, loss of RB has been shown to induce lineage plasticity, which enables resistance to androgen deprivation therapy. This increased understanding of the potential downstream functions of RB in prostate cancer may lead the way to identifying therapeutic vulnerabilities in cells following RB loss.

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Authors and Affiliations

  1. Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA

    Deborah L. Burkhart, Katherine L. Morel, Anjali V. Sheahan, Zachary A. Richards & Leigh Ellis

  2. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

    Leigh Ellis

  3. The Broad Institute, Cambridge, MA, USA

    Leigh Ellis

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  1. Deborah L. Burkhart
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  1. Department of Laboratory Medicine and Pathology, Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Scott M. Dehm

  2. Departments of Urology, and Biochemistry & Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Donald J. Tindall

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Burkhart, D.L., Morel, K.L., Sheahan, A.V., Richards, Z.A., Ellis, L. (2019). The Role of RB in Prostate Cancer Progression. In: Dehm, S., Tindall, D. (eds) Prostate Cancer. Advances in Experimental Medicine and Biology, vol 1210. Springer, Cham. https://doi.org/10.1007/978-3-030-32656-2_13

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