Abstract
The phosphatidylinositol 3'-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway contributes to prostate cancer progression and transition to androgen-independent disease. Furthermore, recent microarray analysis demonstrates that this pathway is often deregulated during prostate cancer progression. Thus, targeting of PI3K/AKT/mTOR may present a promising therapy for castration-refractory prostate cancer (CRPC). In recent years, several interesting strategies have been developed that interfere with distinct components of the PI3K/AKT/mTOR cascade. This article discusses many of the mechanisms involved, specifically in the context of prostate cancer. In addition, we present an overview of preliminary data on the activity of mTOR inhibitors and on the key steps to evaluate which of these compounds are most suitable for the treatment of prostate cancer. Particular emphasis is also placed on the development of novel perspectives to improve the poor prognosis of patients with CRPC.
Keywords: AKT, hypoxia, mTOR, PI3K, prostate cancer, signaling, therapy
Current Cancer Drug Targets
Title:Perspectives on mTOR Inhibitors for Castration-Refractory Prostate Cancer
Volume: 12 Issue: 8
Author(s): Salvatore L. Burgio, Francesco Fabbri, Ian J. Seymour, Wainer Zoli, Dino Amadori and Ugo De Giorgi
Affiliation:
Keywords: AKT, hypoxia, mTOR, PI3K, prostate cancer, signaling, therapy
Abstract: The phosphatidylinositol 3'-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway contributes to prostate cancer progression and transition to androgen-independent disease. Furthermore, recent microarray analysis demonstrates that this pathway is often deregulated during prostate cancer progression. Thus, targeting of PI3K/AKT/mTOR may present a promising therapy for castration-refractory prostate cancer (CRPC). In recent years, several interesting strategies have been developed that interfere with distinct components of the PI3K/AKT/mTOR cascade. This article discusses many of the mechanisms involved, specifically in the context of prostate cancer. In addition, we present an overview of preliminary data on the activity of mTOR inhibitors and on the key steps to evaluate which of these compounds are most suitable for the treatment of prostate cancer. Particular emphasis is also placed on the development of novel perspectives to improve the poor prognosis of patients with CRPC.
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Cite this article as:
L. Burgio Salvatore, Fabbri Francesco, J. Seymour Ian, Zoli Wainer, Amadori Dino and De Giorgi Ugo, Perspectives on mTOR Inhibitors for Castration-Refractory Prostate Cancer, Current Cancer Drug Targets 2012; 12 (8) . https://dx.doi.org/10.2174/156800912803251234
DOI https://dx.doi.org/10.2174/156800912803251234 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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