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Review
. 2009 Mar;9(2):237-49.
doi: 10.2174/156800909787580999.

Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway

Todd M Morgan  1 , Theodore D Koreckij, Eva Corey
Affiliations
Review

Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway

Todd M Morgan et al. Curr Cancer Drug Targets. 2009 Mar.

Abstract

A large number of novel therapeutics is currently undergoing clinical evaluation for the treatment of prostate cancer, and small molecule signal transduction inhibitors are a promising class of agents. These inhibitors have recently become a standard therapy in renal cell carcinoma and offer significant promise in prostate cancer. Through an understanding of the key pathways involved in prostate cancer progression, a rational drug design can be aimed at the molecules critical to cellular signaling. This may enable administration of selective therapies based on the expression of molecular targets, more appropriately individualizing treatment for prostate cancer patients. One pathway with a prominent role in prostate cancer is the PI3K/Akt/mTOR pathway. Current estimates suggest that PI3K/Akt/mTOR signaling is upregulated in 30-50% of prostate cancers, often through loss of PTEN. Molecular changes in the PI3K/Akt/mTOR signaling pathway have been demonstrated to differentiate benign from malignant prostatic epithelium and are associated with increasing tumor stage, grade, and risk of biochemical recurrence. Multiple inhibitors of this pathway have been developed and are being assessed in the laboratory and in clinical trials, with much attention focusing on mTOR inhibition. Current clinical trials in prostate cancer are assessing efficacy of mTOR inhibitors in combination with multiple targeted or traditional chemotherapies, including bevacizumab, gefitinib, and docetaxel. Completion of these trials will provide substantial information regarding the importance of this pathway in prostate cancer and the clinical implications of its targeted inhibition. In this article we review the data surrounding PI3K/Akt/mTOR inhibition in prostate cancer and their clinical implications.

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Fig. (1)
Fig. (1)
PIK3/Akt/mTOR Pathway.
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References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer Statistics, 2008. CA Cancer J. Clin. 2008;58:71–96. - PubMed
    1. Garcia J, Danielpour D. Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies. Mol. Cancer Ther. 2008;7:1347–1354. - PMC - PubMed
    1. Li L, Ittmann M, Ayala G, Tsai M, Amat OR, Wheeler T, Miles B, Kadmon D, Thompson T. The emerging role of the PI3-K-Akt pathway in prostate cancer progression. Prostate Cancer Prostatic Dis. 2005;8:108–118. - PubMed
    1. Majumder PK, Sellers WR. Akt-regulated pathways in prostate cancer. Oncogene. 2005;24:7465–7474. - PubMed
    1. Nelson E, Evans CP, Mack PC, Devere-White R, Lara PJ. Inhibition of Akt pathways in the treatment of prostate cancer. Prostate Cancer Prostatic Dis. 2007;10:331–339. - PubMed

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