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PI3K-mTOR in Cancer and Cancer Therapy pp 263–289Cite as

The PI3K-mTOR Pathway in Prostate Cancer: Biological Significance and Therapeutic Opportunities

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Despite the recent development of new and improved surveillance and treatment strategies, lethal prostate cancer (PCa) phenotypes with castration resistance (CRPC) and metastatic lesions remain poorly understood. Evidence is emerging for the key role of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway in CRPC, which is prevalently dysregulated in advanced PCa. Preclinical studies have revealed a mechanistic interplay between the PI3K/AKT/mTOR pathway and androgen receptor (AR) signaling, a master regulator governing PCa development and progression. The significance of the PI3K/AKT/mTOR pathway in integrating growth signals from crucial cellular events such as protein synthesis, energy metabolism, and cell proliferation and differentiation provides a clear rationale for the development of PI3K/mTOR inhibitors targeting this pathway. Relevant clinical trials offer great potential for clinical benefit. Here, we review the role of the PI3K/AKT/mTOR pathway in PCa and discuss the development and use of pathway inhibitors as single or combined therapies, and highlight ongoing clinical trials for the treatment of PCa.

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  1. Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Jason Boyang Wu & Leland W.K. Chung

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  1. Oncology, Head of Cancer Biology, Avera Cancer Instit Center for Precision, SIOUX FALLS, South Dakota, USA

    Nandini Dey

  2. Oncology, Head of Translational Oncology, Avera Cancer Institute Center for Preci, Sioux Falls, South Dakota, USA

    Pradip De

  3. Precision Oncology,, Avera Cancer Institute Center for, Sioux Falls, South Dakota, USA

    Brian Leyland-Jones

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Wu, J.B., Chung, L.W. (2016). The PI3K-mTOR Pathway in Prostate Cancer: Biological Significance and Therapeutic Opportunities. In: Dey, N., De, P., Leyland-Jones, B. (eds) PI3K-mTOR in Cancer and Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-34211-5_9

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