Cancer cells have epigenetic changes to their DNA. One of these causes the turning off (silencing) of tumor suppressor genes, a small set of genes involved in cell cycle control. Sriharsa discusses drugs currently in the clinic that are able to demethylate DNA and improve the lives of cancer patients.
Sriharsa Pradhan PhD:
For a number of years, scientists have looked into the genetic changes and epigenetic changes that happens in the cancer cells, or the cells, which are derived from cancer, cell culture, which are derived from the cancer cell line, and the first thing they saw is that a lot of tumor suppressor genes. These are a very small set of genes, which are responsible for proper cell cycling, and they saw that this sort of genes are actually silenced, and their promoter regions are methylated; this is a very old, classical way. And as I said, that methylation brings gene silencing, so these genes have no transcript, no proteins.
So, the time passed and everybody thought, "Is it a cause phenomemon, because of the disease they are methylated, or because they're methylated the disease has occurred?" So, there was a lot of controversy in this area until Steve Baylin from Johns Hopkins, and Peter Jones from University of Southern California, they started working on both the DNA modification and histone modification, and trying a drug called 5-aza-deoxycytidine. Now, this is a drug that actually can take how, where the methylation group on the DNA.
And then, once this drug is treated onto the culture cells, you will see the genes that were silenced, now they started working again. So, the genes, like tumor-suppressor genes, which were completely silences on some of the cancer cell line, they started working. And that gives a little confidence and concept that epigenetics is something you can actually write on the DNA and you can erase too.
So, a cell is defective, you can correct it. So, in a broader sense of the cancer therapy region, if you look into the epigenetic gene silencing ... actually, you don't have to look at a surgical, or radiation type of things. You can actually take those tumor cells and you can correct them by using an appropriate drug that can revert back the original state, up to an extent where the cell is going to function in more normal manner, rather than a cancer manner.
And this was something which a lot of traditional physicians and cancer scientists didn't believe before that, until epigenetic drugs are available and been used in clinics. Now there are histone deacetylase inhibitors are available in the clinic. DNA demethylators are available in the clinic and which have actually made a lot of persons' life pretty good. They can live longer.