Oncotarget

Interview with Dr. Benjamin Purow from the Department of Neurology, University of Virginia

The cover for issue 18 of Oncotarget features Figure 5, "Simvastatin prolonged survival, inhibited TGF–β signaling and prenylation, and induced apoptosis and autophagy in vivo," by Xiao, et al.

In this article the researchers noted that statins reduced TGF–β activity , cell viability and invasiveness, Rho/ROCK activity, phosphorylation and activity of the TGF–β mediator Smad3, and expression of TGF–β targets ZYX and SERPINE1 in GBM and GBM-initiating cell lines.

Statins were most potent against GBM, GIC, and other cancer cells with high TGF–β activity, and exogenous TGF–β further sensitized mesenchymal GICs to statins.

Dr. Benjamin Purow from the Departments of Neurology, University of Virginia , Charlottesville, VA 22908, USA said "The statins inhibit the HMG-CoA reductase enzyme and are among the most widely-prescribed drugs in the world for their cholesterol-lowering function. "

Unfortunately, targeting TGF–β signaling, and the mesenchymal cancers with elevated activity, has been hampered by the absence of TGF–β inhibitors in the clinic.

The CellMiner online tool enabled the authors to discover that cancer cell line sensitivity to several statins in the compound library correlated with the expression of certain TGF–β target genes and mesenchymal genes.

This suggested that TGF–β activity might sensitize to the statins, as well as hinting that the statins could be functioning as TGF–β inhibitors.

The research team therefore evaluated in GBM, a cancer in dire need of new therapeutic approaches and in which TGF–β plays an oncogenic role, whether the statins interacted with TGF- activity at physiologically relevant concentrations.

This work is the first to show potent TGF–β inhibition by the statins in GBM and other cancers, and further indicates that TGF–β inhibition is the key mechanism for direct anti-cancer activity of the statins.

The Purow research team concluded in their Oncotarget Research Paper that, with TGF–β inhibitors long anticipated and with candidates in the pipeline, it will be particularly important to test the relationship between statin use and TGF–β pathway activation in patient GBM specimens and to rigorously determine if BBB-penetrating statin use associates with a survival advantage in GBM patients.

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DOI - https://doi.org/10.18632/oncotarget.26733

Full text - https://www.oncotarget.com/article/26733/text/

Correspondence to - Benjamin Purow - bwp5g@virginia.edu

Keywords - statin , glioblastoma , TGF-beta , SMAD3 , RhoA/ROCK

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