EACR 21, 26—29 June 2010, Oslo

Interview with Dr Peter Jones (University of Southern California, USA)

The potential of epigenetics in cancer treatment

The last 25 years in cancer research has really been preoccupied with genetic changes which drive cancer formation. For example, mutations in genes which mean that the gene doesn’t work properly or losses of genetic information, or bits and pieces of genetic information being moved from one place to another, giving rise to a dis-regulation which causes cancer.

What’s become now apparent is that there is this epigenetic process which really refers to silencing of genes or activating genes when they either should be off or on. So it’s a series of switches which keeps genes off which should be on or keeps genes on which should be off. So this mechanism is actually now understood and I talked about various ways at a molecular level that genes become silenced. Now this is, of course, essential for normal development, for example in the inactivation of the X chromosome. You have to have a way in a cell that you can switch off something over a long period of time. So without the switches we wouldn’t be able to live but what happens is the switches can go wrong and so the genes which are relevant to cancer formation get inappropriately switched off.

Now the huge advantage from a therapeutic standpoint is that you still have a perfectly good gene in the cell but it has been turned off. So if you can turn it back on again you could make the cell go one step back and maybe start behaving more like a normal cell. So we have a series of drugs which have just been approved over the last five years by the Food and Drug Administration, which actually can unlock these genes and turn them back on again. There are four of them available right now and they’re being used to treat various kinds of haematological malignancies such as myeloid dysplastic syndrome or the other one is cutaneous T-cell lymphoma.

These particular kinds of cancer are fairly rare and what we hope to do over the next few years is to be able to extend the promise of epigenetic therapy, as we call it, into the treatment of solid tumours. So I showed some preliminary data from colleagues of mine which suggests that this might actually work in even late stage lung cancer, which is an incredibly difficult disease to treat.

Mostly we focus on genes which have become switched off and so in any given cancer cell there are a lot of genes, maybe as many as 5% of all the genes in the cell, which have become switched off when they should be on. Those are actually the ones that we target with this kind of therapy, we try and turn them back on again.

These are tumour suppressor genes?

Yes, so several tumour suppressor genes, DNA repair genes, genes which hold cells together, genes which control when cells die, those genes become switched off and the cancer cell uses the switching off to allow the cancer cell to divide inappropriately and to escape therapy. So the whole idea is by turning them back on again we can do something good for the patient.