Study provides novel mechanism of action of anti-cancer compound: perifosine

Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that an article published in the May 2012 issue of Plos One, outlines a novel mechanism of action of the Company's oral anti-cancer compound, perifosine, which could provide a rationale for a novel approach to the treatment of Malignant Pleural Mesothelioma (MMe), an aggressive type of cancer associated with exposure to asbestos. The article titled, "Perifosine as a Potential Novel Anti-Cancer Agent Inhibits EGFR/MET-AKT Axis in Malignant Pleural Mesothelioma", G. Pinton, A. Gabriella Manente, G. Angeli, L. Mutti, L. Moro, is available at www.plosone.org. Plos One is an international, peer reviewed on-line publication.

Methods

Perifosine's activity was tested on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy.

Results

Data demonstrated that perifosine caused a dose-dependent reduction of Akt activation, at concentrations causing MMe cell growth arrest. Moreover, data described a novel mechanism of perifosine that interferes, upstream of Akt, affecting EGFR and MET phosphorylation. Finally, data demonstrated a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin.

Conclusions

This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-Akt1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe.