Epigenome deregulation in cancer

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Published: 6 Jan 2015
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Dr Zdenko Herceg, International Agency for Research on Cancer (IARC), Lyon, France

Dr Herceg speaks to ecancer at the 2nd EurocanPlatform Translational Research Course, discussing his presentation on his work within the field of epigenetics and how it has transformed our understanding of the causes of cancer. 

He highlights its role in cancer prevention and how epigenetic regulation has been shown to be present across all cancer types.

Learn more about the EurocanPlatform project here

My presentation was focussed on epigenetics and epigenetics is a relatively new, emerging field, a rapidly expanding field of modern biology that has already made an important, or I would say tremendous, impact on our thinking and understanding the causes of cancer. So the epigenetics refers to the stable and heritable changes in gene expression and phenotypic changes that are not coded in DNA. Another defining feature of epigenetic events is their intrinsic reversibility and therefore there is enormous interest for clinics, specifically for finding the drugs that can target epigenetic events in cancer or pre-cancerous lesions and therefore to have a therapeutic benefit.

What were the main messages of your talk?

That the epigenome can be considered as a kind of interface between the genome and the environment. Therefore the epigenome on one hand buffers the influence of the environment and on the other hand it actually modulates response to the environmental stresses. Most cancers are environmentally induced and therefore potentially preventable. Therefore looking at the epigenome, understanding the epigenome deregulation in the cancer has an impact, of course, for understanding the mechanisms of carcinogenesis but also for developing the strategies for cancer treatment, developing the biomarkers for early detection but also, most importantly probably, is cancer prevention. This is one of our focuses, basically, to try to understand the deregulation of the epigenome in response to environmental factors and also to provide the basis for developing strategies for cancer prevention as well as treatment, of course, and early detection.

What is the significance towards clinical practice?

First of all, all these major international sequencing efforts reveal that the epigenome deregulation is present in virtually all cancer types. There was lots of healthy scepticism in the past whether epigenetics is a cause or consequence of cancer development. Now there is hard genetic evidence that the epigenome is not only important but actually that epigenetic deregulation is present in virtually all cancer types. Therefore, it is important to understand the functional impact of this deregulation and also in devising the strategies for treatment it is important to keep this in mind. Because of these new concepts, so conceptual breakthroughs but also, I would say, almost spectacular advances in technology that allows the profiling of the epigenome in high throughput and genome wide settings, allows us to actually understand but also to devise drugs, smart drugs or epigenetics based drugs, to treat the cancer. Many agents actually are currently in clinical trials to target specific epigenetic events and already there are several agents that are actually based on epigenetics that are used in a clinical trial, in the clinics, to treat specific cancer types. So there is more… I would say in the near future we will see more of these drugs and their utility in clinical practice.

There are many other areas that are important when you talk about epigenetics. Of course, that is biomarker discoveries; there is more increasing evidence that the epigenetic events are occurring early in cancer development therefore it is important to look at the epigenome for the biomarker development but also for cancer prevention.

What are the main obstacles that you have encountered?

We look at the cancer genome and epigenome and we will see that in virtually all cancers, all tumours, all types of tumours, we see a range of genetic and epigenetic events. But the real challenge is to identify functionally important, also called driver, events and distinguish them from merely non-functional passengers. So that’s an important challenge and one of our lines of research is going into this direction to identify the driver events and their functional impact on cancer development. Another challenge is, of course, as we are applying this new powerful tool that will generate large, comprehensive datasets, the challenge is to integrate this data and interpret this data, also how to translate this new knowledge into practice or into the strategies for cancer treatment and cancer prevention.

So there are many challenges ahead but we are making significant progress and this field is holding a promise to advance not only knowledge but also to advance the strategy for cancer treatment and prevention.

What are the next steps?

The two main areas that we are focussing on, one is of course to understand the mechanism by which environmental factors, as I mentioned earlier, most cancers are potentially preventable and they’re induced by environmental factors, lifestyle factors. Therefore our challenge would be to identify changes, epigenetic changes that are associated with the environmental and lifestyle factors. Of course this has an impact on prevention because if you know the causes then we can prevent… we know that this is not as simple, even if you know, but if you don’t know the causes of this we cannot prevent or design a strategy, an efficient strategy, for prevention. The second challenge is, of course, to use this knowledge in what we call carcinogen identification and classification; this is an important programme in our institute. Another area of research is biomarkers, so the biomarkers to exposure, biomarkers of cancer risk. And the epigenome, looking at the epigenome, is important to identify those biomarkers of cancer risk that may be used for further studies or that are of direct relevance to the studies of cancer prevention and carcinogen identification.

I will just say that cancer research is increasingly multidisciplinary and it is important that we work with other experts or other professionals and that we work more closely with bioinformaticians, for example, that are obviously essential to help us to interpret, integrate interpreting epigenomic data, but also to work with epidemiologists that are co-ordinating large prospective cohorts that can, of course, help us to identify the causes. But also the knowledge needs to be translated into clinical practice so there is an opportunity to work with the clinicians as well and to validate the markers, also to try to translate the knowledge that we are generating more using these new approaches, using the different models and laboratory science in general.