What are hypomethylating agents and when are they used?

What are hypomethylating agents and when are they used? Hypomethylating agents are low dose chemotherapy drugs that go into the DNA and the RNA of the cancer cells and turn on and turn off genes. They remove these groups called methyl groups that sit on the DNA and prevent it from transcribing into RNA and proteins. So by altering essentially the DNA-RNA interactions in the cells, they turn on genes that have been turned off in the process of the leukemia and allow normal hematopoiesis and normal count recovery to occur. We typically use these hypomethylating agents in pre-leukemic states like myelodysplastic syndrome. They're not killing cells. They don't work like conventional chemo by killing cells. They work by altering the DNA. So I tell my patients, it's like you're trying to reform the bone marrow. You're not trying to kill it off. So the hypomethylating agents in the past have taken a while to work and you need to give them continuously because they're not killing it. There needs to be constant administration. We typically do that type of therapy on a monthly basis. That's been our go-to for older unfit patients as a single agent, a society needing to decide to be for a couple years now. But the overall response rates have been slow, 20, 30 percent. We are now using the hypomethylating agents as like a backbone drug to combine with other targeted therapies because it is generally well tolerated and can be given easily in the outpatient setting.