Skip to main content
Journal cover image

Perifosine: update on a novel Akt inhibitor.

Publication ,  Journal Article
Gills, JJ; Dennis, PA
Published in: Curr Oncol Rep
March 2009

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Curr Oncol Rep

DOI

EISSN

1534-6269

Publication Date

March 2009

Volume

11

Issue

2

Start / End Page

102 / 110

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase Inhibitors
  • Phosphorylcholine
  • Oncology & Carcinogenesis
  • Neoplasms
  • Membrane Microdomains
  • Humans
  • Clinical Trials as Topic
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gills, J. J., & Dennis, P. A. (2009). Perifosine: update on a novel Akt inhibitor. Curr Oncol Rep, 11(2), 102–110. https://doi.org/10.1007/s11912-009-0016-4
Gills, Joell J., and Phillip A. Dennis. “Perifosine: update on a novel Akt inhibitor.Curr Oncol Rep 11, no. 2 (March 2009): 102–10. https://doi.org/10.1007/s11912-009-0016-4.
Gills JJ, Dennis PA. Perifosine: update on a novel Akt inhibitor. Curr Oncol Rep. 2009 Mar;11(2):102–10.
Gills, Joell J., and Phillip A. Dennis. “Perifosine: update on a novel Akt inhibitor.Curr Oncol Rep, vol. 11, no. 2, Mar. 2009, pp. 102–10. Pubmed, doi:10.1007/s11912-009-0016-4.
Gills JJ, Dennis PA. Perifosine: update on a novel Akt inhibitor. Curr Oncol Rep. 2009 Mar;11(2):102–110.
Journal cover image

Published In

Curr Oncol Rep

DOI

EISSN

1534-6269

Publication Date

March 2009

Volume

11

Issue

2

Start / End Page

102 / 110

Location

United States

Related Subject Headings

  • Signal Transduction
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase Inhibitors
  • Phosphorylcholine
  • Oncology & Carcinogenesis
  • Neoplasms
  • Membrane Microdomains
  • Humans
  • Clinical Trials as Topic
  • Animals