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Current Oncology Reports

, Volume 11, Issue 2, pp 102–110 | Cite as

Perifosine: Update on a novel Akt inhibitor

  • Joell J. Gills
  • Phillip A. DennisEmail author
Article

Abstract

The PI3K/Akt/mTOR pathway is aberrantly active in most human cancers and contributes to cell growth, proliferation, and survival. Akt is a nodal regulator of cellular survival pathways and an attractive target in cancer therapy. Many inhibitors of Akt are being developed. Perifosine is an oral Akt inhibitor currently being tested in phase 2 clinical trials. Unlike most kinase inhibitors, which target the adenosine triphosphate-binding region, perifosine targets the pleckstrin homology domain of Akt, thereby preventing its translocation to the plasma membrane. Single-agent activity with perifosine has been observed in sarcoma and Waldenström macroglobulinemia patients. However, the disappointing response rates of common solid tumors to perifosine as a single agent have diminished expectations and prompted further investigation into its mechanism of action. Perifosine exerts Akt-dependent and Akt-independent effects, and although many preclinical studies have documented Akt inhibition by perifosine, clinical validation of these findings is lacking. In this article, we review the clinical history of perifosine and discuss its many biologic activities.

Keywords

Multiple Myeloma Clin Oncol Bortezomib Lipid Raft Lenalidomide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Current Medicine Group LLC 2009

Authors and Affiliations

  1. 1.Medical Oncology BranchNational Cancer InstituteBethesdaUSA

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