What are hypomethylating agents?

These are not a new class of drugs.

Essentially, these are what we call;
they belong to nucleoside analogues family.

At the beginning, when they start the drug development,
we usually would try to go to the maximum authority dose.

So in cancer treatment, we try to go up, up, up for the dose
that we get to the point where the drug is toxic.

We cannot proceed any further.

By doing so, we discovered these drugs are being toxic.

But then what?

Why do we need them for?

Because already we have toxic drugs
such as cytarabine that can really kill the cells.

But then investigators went back and they discovered
the drugs can be effective at a lower dose.

And that is what they called hypomethylating effect.

So what [does] that stand for and how does it work? 
And, here, I will go into how these drugs

work compared to other chemotherapy.
There’s something called epigenetics.

Essentially, when we are born, our genome,

the genes we have are same whether we're in eye cell

or a kidney cell or a skin cell, liver cell,
but yet they function differently.

What that means, I mean, certain genes that we need to
function in the liver, that we do not need them in a brain.

They silence in the brain and vice versa.

There's a process called silencing that happens early

on—at the conception—from the first day of life.

And then there's silencing happening,
which is a normal process.

But then our body has certain genes
that are supposed

to suppress cancer from happening.

They watch over abnormalities of the cells.

Imagine these abnormal genes are being silenced.

If they’re silenced, they cannot do the role.

And therefore why they’re silenced

because among others, they have methyl group
that get attached to this part of the gene.

When we went back to these quote unquote

hypomethylating agents, we discovered that the lower dose
they can remove the methyl group

and let the gene express itself.

And as such it can suppress the development of cancer.

And that is what hypomethylating agents [are].

Therefore, they are not a strong chemotherapy,
but they have a specific effect

to express certain genes supposed to be expressed.

But for a reason or another, were silenced and cancer took place.

That in a simple mechanistic way, how these drugs work.