2010 American Society of Hematology Annual Meeting 3rd - 7th December
Interview with Prof Stephen Baylin - Johns Hopkins University, Maryland, USA
The role of epigenetics in cancer treatment
SB Stephen Baylin
IV Okay, so thanks for joining us here at ASH 2010. Can you tell me a bit about the talk you were giving this morning?
SB So, I gave a talk in a session today that was related to what’s called epigenetic abnormalities of cancer. So, I guess it’s first we have to define epigenetics a little bit. So, genetics refers to your DNA and in cancer I think most people know that you get mutations, and those mutations can disrupt the proper function of genes. So, DNA is like the hard drive and it has all the information in it to specify for everything ourselves do both normally and abnormally. Epigenetics, but the hard drive needs software, and epigenetics is kind of like the software because it’s the way the cell wraps up the DNA inside itself around structures called nucleosomes. But it’s packaging, it’s basically the way the DNA is packaged that tells the DNA how to function. So, epigenetics is the packaging basically. And just like you can get mutations that damage the hard drive, you can alter the packaging so the hard drive’s all right underneath but the packaging is not functioning properly. And the abnormal packaging can lead to genes dysfunctioning in cancer where the gene underneath is fine but it’s not being talked to properly. And so the hope is it’s hard to repair the hard drive that can be permanently damaged. But epigenetics, you can reverse it. So, if you can send the abnormal packaging back to normal packaging you can restore the function of the abnormal genes. And this is what the importance to cancer is and there is a whole attempt which is gaining some traction to employ drugs which are called epigenetic therapies. They are trying to reverse the abnormalities of packaging back to normal. So, this is basically what the whole theme of the conference was I was talking in this morning.
IV And what sorts of drugs are we talking about?
SB So, the genes that we study primarily they’re abnormal, epigenetically get turned off. The cell should be able to use them but it can’t because they’re abnormally packaged. And many of these genes are what are called tumour suppressers. In other words if the cell can turn them back on this would be a block to cancer. But because the cell can’t do that, it helps the cancer roll along from the very earlier stages to the later stages. So, one of the processes that allows epigenetics to turn off a gene inappropriately is to do something called methylated DNA. Areas where the DNA should not be methylated get methylated and that helps turn the genes off. So, one of the class of drugs that’s been employed in the clinic are agents that are called demethylating agents, DNA demethylating agents. They can reverse the abnormal DNA methylation and theoretically bring genes on that should be available where they’ve been silenced. So, there are drugs called Vidaza or Dacogen that are out there. They’ve had some success in the leukemic type of diseases and they’re more now being studied as well in the common cancers such as lung, colon and breast. And our job is to figure out if they’re working because they’re affecting epigenetics, and what are the diseases that we can affect if we treat with drugs like that. And I talked a bit about that arena this morning.
IV And can we use epigenetics to better get drugs that are already existing to better reacts with things like circulating tumour cells and things like that?
SB Well, that’s a great question and from what we’ve studied in the laboratory one of the best use of these drugs that DNA demethylate, may be not just to use them for their own effects, but it looks as if by manipulating these genes we may sensitise cancer cells to other agents that are already out there, or there may be new combinations of agents that also affect epigenetics that can be used with. So, I think this is one of the very promising uses in the future. For example, you could be giving patients’ chemotherapy, we know often that you can get an effect from chemotherapy, when you stop it the tumours may come back, you get a resistance. Could we use the agents I was talking about to follow the chemotherapy in such a way that we prevent that recurrence. We block some of the chemotherapy resistant cells and turn them in a direction so that now they stay away longer. And that is something that we’re studying very intensely.
IV And is there the potential for using Omix in the same way that we use it for genetics, for epigenetics as well?
SB Another great question. That’s exactly what has come to the fore for this area of epigenetics in the last five to seven years especially. So, you not only can study them for individual genes, what is the epigenetics of that gene, but now we can go across what we call the epigenome. You can map across the whole area of DNA where the various epigenetic processes are occurring. And we’re using those to say, well how does cancer look epigenomically relative to normal cells. And when we use these drugs how can you switch the whole epigenome around to look like a more normal cancer epigenome back to a more normal epigenome. So, that’s really come in to play in the same way Omix has been used to pick up genetic changes in the past.
IV And were you hoping will be the impact in the clinic?
SB Well, I think we’ve come to understand over the past decade or more that cancer is an interplay between genetic abnormalities and epigenetic abnormalities. Even some mutations that they’re finding now, the end result of the mutation is to alter the epigenetics. And the epigenetics may be the most… the easiest, not easy, but the easier abnormal process to reverse. So, we’re thinking that this is going to be a very prominent role in cancer management, is to understand this epigenome and to use the drugs we already have plus new drugs, plus help the older drugs as you’ve talked about to really be a cancer and management strategy. So, there’s a lot of excitement right now. I think over the next years we’ll see how much of that excitement pans out, but the potential is real and that’s why they have a conference on it, or particular sessions on it at this meeting.
IV And finally, why would a patient be interested in this particular area of research?
SB Well, let me tell you right now in the States, and I think it will come to fore in Europe as well, we have a big project sort of mission that’s called the stand up to cancer. There are five teams that are approaching various new ways to manage cancer. We have the team on epigenetic therapy, and it’s based on early information that in a very difficult disease and common disease situation advanced lung cancer. We’re able to use these agents that we’ve been talking about and get subsets of patients to have robust responses. So, this is letting the stand up to cancer to trials not only in lung cancer late stage and early, but now colon and breast cancer are starting. So, these trials are going to be available to patients and there’s real potential, and so patients with advanced disease right now particularly these trials are going to be open to them. So, the patients have heard about these and they’re getting very interested in this, and we’re very eager to enrol patients on those trials. And there are other trials in epigenetics going on as well. So, I think it’s of vast importance to patients right now to be aware of this and consider that as a possibility if unfortunately other therapies have failed. And hopefully in the future maybe these will be frontline therapies that patients may be able to avail themselves of.
IV It will be interesting to see how it progresses. Thank you very much.
SB It will be to all of us who are in it and hopefully all the patients who may participate in things like this as well.
IV Okay, well thanks for your time.
SB Thanks for asking me.