Dominic D'Agostino

That has never been done.

So you want to do that.

And then that is not alone.

So what I'm talking about here is an adjuvant to the standard of care.

So achieve a GKI of one to four, maintain that.

And then you go,

and aggressively target glucose and glutamine.

So you could target glucose with lonidamine, it's a hexokinase inhibitor, 3-bromopyruvate, 2-deoxyglucose.

You can use an SGLT2 inhibitor.

You can use, I mean, we have about two dozen different drugs that you could use and off the shelf kind of things like SGLT2.

And then you want to target glutamine because you could take glucose out of cell media and put in glutamine and maintain cancer cells in glutamine without glucose.

I know.

I

But the idea then is to use something like lonidamine, like inhibit hexokinase 2.

There are enzymes, glycolytic enzymes that are upregulated.

There are transporters that are upregulated.

And if you create an energy crisis in GBM cells that's great enough, then you trigger autophagy and then you trigger...

cell death because there's an incredible glycolytic energetic demand in glioblastoma cells.

And if that demand is not met, then that triggers cell death pathways.

But to make inroads into that and create that energetic crisis, you have to decrease glucose availability, decrease circulating insulin, which decreases growth factors like IGF-1 and a whole host of other mTOR and other growth factors.