EACR 21, 26—29 June 2010, Oslo

Professor Kristian Helin (University of Copenhagen, Denmark)

The development of novel targets for cancer therapy

What we’re working on is basically trying to identify novel targets for cancer therapy. In the last five to seven years we’ve worked in the area called epigenetics; we think that epigenetics is extremely interesting because it’s involved in the regulation of normal cell differentiation and cell fate decisions. Many different laboratories have found that the enzymes which are involved in that process, very often they are deregulated in human cancer and that’s why that area is booming at the moment. Recently there have been two new, novel therapies based on these enzymes, one targeting DNA methyltransferases and the other one targeting histone deacetylase, so H-stacks. Those new drugs are being used for cutaneous T-cell lymphomas and MDS patients as well.

What has happened now is that novel enzymes which are involved in epigenetic relations which have also been shown to be involved in cancer, that they are characterised, we know much more about the molecular mechanisms. We show how they work in cancer biology and we hope that within the next some years we will start identifying novel interesting inhibitors which can be used for new cancer therapy. We think that they will be more specific than what we’ve seen before because we can go specifically in and target subgroups of these new enzymes.

So we think that they will be more specific because we can make them, like for kinase inhibitors, specific for different sub-families but obviously we also think that there might be toxic side effects of those inhibitors. We think some of them will be mostly related to developmental functions and as human adults have developed at that point so perhaps we will see lower toxicity than just general DNA synthesis inhibitors.

Are there any on-going early phase trials for these types of drugs?

There are not yet; most of them are in pre-clinical trials. For the histone methyltransferases there have been very nice inhibitors properties which I expect to be in pre-clinical trials and soon we’ll go into phase I clinical trials. The histone demethylators we’ve only known for a few years now so it’s early days, actually, to take it all the way to phase I clinical trials.

But what is interesting is that several bio-tech companies have been founded in the last three or four years based on the idea that you can target this sub-class of enzymes which are involved in epigenetics. Basically all major big pharmaceutical companies are working in that space.

These enzymes will be across many types of cancer?

So far we have very strong evidence for deregulation in all hematopoietic cancers – in breast cancer, in prostate cancer and all the major cancer types we’ve seen deregulation of these enzymes, either by over-expression, gene amplification or expression of fusion proteins.

So once a drug is identified it can be used for many types of cancer?

Yes, what I would foresee is that the clinical trials will be used in those cancers where there is most evidence for the role of this and where there are good biomarkers for the inhibition of those enzymes. The clinical trials will be on those first and therefore we are going to see the approval, hopefully, in some years of some of those new specific inhibitors.