How epigenetic changes could transform cancer treatment

Although one in two people will develop a form of cancer during their lifetime, much about the disease remains unknown. Ongoing research is steadily revealing more about cancer biology, however, and a recent finding may even reshape how we understand the development of cancers.

Before examining that discovery, it is useful to consider the established explanation for the conversion of normal cells into cancer cells. This traditional theory holds that DNA mutations are the main cause of cancer.

Ageing and certain lifestyle or environmental influences, including smoking and UV radiation, are known to produce random DNA mutations, also called genetic alterations, within our cells. The majority of these genetic alterations either cause cells to die or have no effect at all.

A small number of mutations, however, support a cell's survival. When enough "life extending" DNA mutations build up in one cell, it can become effectively immortal. It then begins to divide uncontrollably, creating a cancer. Considerable experimental evidence supports this theory.

Yet this explanation gives DNA mutations a central role, despite the fact that they are permanent and frequently hard to target with medicines. If genetic mutations alone cause cancer, our capacity to destroy cancer cells could therefore be restricted.

Other explanations for the origins of cancer are particularly interesting. If they are also correct, they may lead to improved methods for preventing and treating cancers.

Genetics and epigenetics in cancer development

Researchers tested one such theory in a recent publication in Nature. Their study used fruit flies, which share 75% of the genes linked to human diseases.

Using these flies, the team examined whether cancers might result from epigenetic changes: reversible "marks" added to the genome that switch genes on or off.

While "Genetics" and "epigenetics" sound alike, they describe two very different processes. To see the distinction between genetic mutations and epigenetic alterations, imagine that your DNA is a book containing part of the information required to make you.

In this comparison, every gene is equivalent to a sentence in that book. A genetic mutation is like taking a pen and crossing out or changing a sentence. Once this has happened, it cannot be reversed.

Epigenetic marks involve subtler adjustments, comparable to underlining a sentence in pencil or placing a bookmark so that a particular page can be found quickly. They arise when small molecules are added to or removed from DNA itself, or from proteins that are closely linked with DNA.

Epigenetic alterations can therefore be reversed, but they may profoundly affect how cells "read" DNA.

These marks are vital for switching genes on and off during development, for instance when our eyes form in the womb. They also connect the outside environment with genes. Epigenetic control of genes, for example, helps animals adapt as seasons change.

Fruit fly evidence for epigenetic changes

For many years, epigenetic marks were thought to be too short-lived to cause cancer. Earlier work from our research group, alongside studies by many others, has shown that cancer cells accumulate numerous epigenetic alterations. These alterations can promote cancer cell survival just as effectively as DNA mutations.

This suggests that cancer may arise as both genetic and epigenetic alterations accumulate.

Previous research in this field, however, had not produced enough evidence to show that epigenetic alterations could trigger cancer without DNA mutations.

The recent Nature study has now demonstrated for the first time that a temporary shift in epigenetic marks, even in the absence of a DNA mutation, can be enough to cause cancer.

Treating cancer

As well as being scientifically compelling, this finding could alter the treatment of certain cancers, particularly if later studies confirm the results.

If epigenetic alterations play a part in cancer, researchers may be able to create epigenetic therapies for this deadly disease. Scientists and pharmaceutical companies have pursued this possibility for the past few decades.

Such treatments would reprogramme cancer cells by altering the distribution of reversible epigenetic marks. This could enable cells to return to normal behaviour and, in turn, halt their uncontrolled multiplication.

Some of these emerging epigenetic medicines have already been approved in certain countries to treat blood cancers and sarcomas. Other epigenetic drugs are undergoing clinical trials for the most common forms of cancer, including breast and prostate cancer.

The epigenetic theory of cancer may also affect cancer detection. Cancer cells release traces of abnormal epigenetic marks, which can be identified in the blood of people with cancer.

For this reason, my colleagues and I have described a blood test capable of detecting epigenetic marks from very small blood samples. DNA mutations can also be detected in the blood of cancer patients, so combining genetic and epigenetic testing could make cancer detection still more accurate.

Epigenetic treatments could additionally be used alongside established cancer therapies, such as surgery and radiotherapy, both of which are highly effective in many cases.

Our team has also suggested that epigenetic drugs and tests could eventually support better, more precise treatments tailored to individual patients, although this technology remains a long way from routine use.

Although the epigenetic theory of cancer accounts for important elements of disease progression, it does not mean that the classical cancer theory is incorrect. Instead, it broadens our understanding of a complex process and highlights how much there is still to learn about cancer.

The next stage of this work is to test the epigenetic theory in other models, including human cells, to advance the development of precision treatments.

Francesco Crea, Senior Lecturer in Cancer Genetics, The Open University

This article is republished from The Conversation under a Creative Commons licence. Read the original article.