by Although one in two people will develop some form of cancer in their lifetime, there is still much we do not know about this disease. But thanks to ongoing research efforts, we continue to learn more about the biology of cancer. One of these recent discoveries could change our understanding of how cancer develops.
But before we talk about the new discovery, let’s first discuss the classic theory that tries to explain why cancer cells become normal cells. This theory shows that DNA mutations are the main cause of cancer.
It is well known that random DNA mutations (also known as genetic changes) occur in our cells due to aging, as well as a number of lifestyle and environmental factors (such as smoking and UV radiation). Most genetic changes induce cell death or have no consequence. However, some mutations favor cell survival. If a sufficient number of “life-extending” DNA mutations occur in a cell, this cell will become almost dead – starting a series of uncontrolled duplications that generate cancer. This theory is supported by extensive experimental evidence.
However, this theory places great emphasis on DNA mutations, which are irreversible and often difficult to target with drugs. Therefore, if cancer is caused solely by genetic mutations, our ability to kill cancer cells may be limited.
Interestingly enough, there are other theories about how cancer starts. If these theories are also valid, we could develop better ways to prevent and treat cancer.
Researchers have tested one of these new theories in a recent Nature publication. This study was conducted in fruit flies (which share 75% of the genes associated with human disease). The researchers used the flies to investigate whether cancer could be caused by epigenetic changes – reversible “marks” added to the genome to turn genes on and off.
“Genetics” and “epigenetics” may sound similar, but they represent two very different processes. To understand the difference between genetic mutations and epigenetic changes, think of your DNA as a book that contains some of the information needed to make yourself.
According to this metaphor, each gene would be equivalent to a sentence in this book. A genetic mutation is like using a pen to scratch out or modify a sentence. Once it’s done, you can’t undo it.
Epigenetic marks are more subtle changes – such as highlighting a sentence with a pencil or using a bookmark to quickly retrieve a particular page. These changes are achieved by adding or removing small molecules to the DNA itself, or to the proteins closely associated with DNA. So, epigenetic changes are reversible – but they can have a big impact on the way your cells “read” the DNA.
Epigenetic marks are essential for turning genes on and off during development (such as helping us form our eyes in the womb). Epigenetic marks also form a bridge between the external environment and the genes. For example, epigenetic regulation of genes allows animals to adapt to changing seasons.
For a long time, epigenetic marks were thought to be too fleeting to actually cause cancer. But previous work by our research group and many others has shown that cancer cells accumulate a number of epigenetic changes – and these changes can promote cancer cell survival as effectively as DNA mutations. This would suggest that cancer develops through the accumulation of both genetic and epigenetic changes.
However, previous studies in this area did not have enough evidence to show that epigenetic changes can cause cancer in the absence of DNA mutations. This recent Nature study showed for the first time that a temporary change in epigenetic marks – even without a DNA mutation – is enough to cause cancer.
Cancer treatment
This is not only an interesting scientific finding, but evidence that could change the way certain cancers are treated – especially if these results are confirmed in future studies.
If epigenetic changes contribute to cancer, researchers could develop epigenetic therapies for this deadly disease. Many scientists and pharmaceutical companies have been working on this for the past few years.
These therapies would reprogram cancer cells by altering the distribution of reversible epigenetic marks. This would allow cells to return to their normal behavior, stopping uncontrolled reproduction.
Some of these new epigenetic drugs are now approved in several countries for the treatment of blood cancers and sarcomas. Other epigenetic drugs are in clinical trials for the most common types of cancer – including breast cancer and prostate cancer.
The epigenetic theory of cancer also has implications for cancer detection. Cancer cells release traces of abnormal epigenetic marks and they can be found in the blood of cancer patients. That is why my colleagues and I have described a blood test that can detect epigenetic marks from small amounts of blood. Since DNA mutations can also be found in the blood of cancer patients, cancer detection could be made more accurate by combining genetic and epigenetic tests.
Epigenetic therapies can also be combined with conventional cancer therapies – such as surgery or radiotherapy, which are very effective in many cases.
Our team also suggested that drugs and epigenetic tests could be used to develop better and more precise treatments that are optimized for each patient – although this technology is still a long way off.
Although the epigenetic theory of cancer explains important aspects of how the disease progresses, this does not mean that the classical theory of cancer is wrong. This new theory enriches our understanding of a complex phenomenon, reminding us that there is still much to learn about cancer.
The next steps in this research are to test the epigenetic theory in other models – such as human cells – to advance the development of precise treatments.
This article from The Conversation is republished under a Creative Commons license. Read the original article.
Francesco Crea is currently funded by a Prostate Cancer UK grant to develop epigenetic cancer therapies. He has also received research funding from Belgium’s Volition to test cancer biomarkers.
