Perifosine: Update on a novel Akt inhibitor

Joell Gills, Phillip A. Dennis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)102-110
Number of pages9
JournalCurrent Oncology Reports
Volume11
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

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Waldenstrom Macroglobulinemia
Neoplasms
perifosine
Phosphatidylinositol 3-Kinases
Sarcoma
Cell Survival
Phosphotransferases
Adenosine Triphosphate
History
Cell Proliferation
Cell Membrane
Clinical Trials
Survival
Growth
Therapeutics
Pleckstrin Homology Domains

ASJC Scopus subject areas

  • Oncology

Cite this

Perifosine : Update on a novel Akt inhibitor. / Gills, Joell; Dennis, Phillip A.

In: Current Oncology Reports, Vol. 11, No. 2, 2009, p. 102-110.

Research output: Contribution to journalArticle

Gills, Joell ; Dennis, Phillip A. / Perifosine : Update on a novel Akt inhibitor. In: Current Oncology Reports. 2009 ; Vol. 11, No. 2. pp. 102-110.
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