There are some epigenetically active drugs that have recently been developed. And kind of, it’s difficult to understand exactly what they’re trying to do with these drugs, unless you take a step back and discuss what’s going on in myeloma.
So one of the important features is these chromosomal translocations, where one bit of DNA moves to another region of the genome and overexpresses a gene here...
There are some epigenetically active drugs that have recently been developed. And kind of, it’s difficult to understand exactly what they’re trying to do with these drugs, unless you take a step back and discuss what’s going on in myeloma.
So one of the important features is these chromosomal translocations, where one bit of DNA moves to another region of the genome and overexpresses a gene here. And so assume that this gene is essential to making myeloma cells grow quickly, be resistant to treatment, and you could give it a name, you can call it MYC. And MYC is important than doing that. And so you want to down-regulate MYC, if you can, because the cells will behave better.
And what we know is that in this bit of DNA, that’s moved tends to contain enhancer sequences that overexpress genes when they land next to them. And so the way to control this bit of DNA with kind of molecules that affect transcription factors, transcription, and the enhancer activity of that site. And so really that’s what we’re trying to do with these epigenetically active agents. Like the ones that you described and the BRD4 inhibitors are to down-regulate these enhances, so MYC is down-regulated and the cells behave much better as a consequence of that. And so these drugs do seem to work. It’s a good rationale. It’s a good logic. And by focusing on high risk, it draws attention to genes like MYC, because they’re not so important in the early stages of myeloma, when the cells are behaving much, much better. So we start seeing developing therapies that are active for high-risk disease.