Thursday, 16 August 2012

Her name was Reo and she killed cancer

We live in an ageing population, especially in the developing world. With the huge increase in life expectancy that has been achieved in the previous 100 years, diseases of old age have come to the forefront of medial thinking; none more so than cancer. In the UK alone, roughly 320,500 people were diagnosed with cancer in 2009. I use the UK as an example, as opposed to using a worldwide statistic, since in the developing world a huge proportion of cancer comes from infectious diseases. Cancer causing infectious diseases are much better controlled in the UK and other parts of the developed world, making cancer predominantly a disease associated with age. Cancers related to age form due to mutation of cells caused by so called ‘mutagens,’ such as ultraviolet light (from the sun) or chemicals (eg. in cigarette smoke). Multiple mutations (around 6-7) are needed in order to make a cell cancerous. In order to acquire all of these necessary mutations a cell needs time, which is why cancers can be regarded as a disease of age. The treatment of cancer has dramatically improved in recent times, but we are still without a consistent cure and the treatments which are used are not without some serious side effects. Until a complete cure is found the science world will continue to look for new and improved treatments. To that end, I would like to look at one of the slightly stranger approaches; the deliberate infection of patients with a virus to treat their cancer.

When most people think of viruses the first thought is of disease; viruses such HIV (AIDS), influenza (flu), rhinovirus (colds), and so on, are likely to spring to mind. However the vast majority of viruses on our planet do not cause humans any ailments at all. Many viruses will never come into contact with humans and so never get the chance to cause infection, our immune system keeps many viruses at bay and many viruses do not grow well in human cells; to cite just a few reasons as to why the majority of viruses have little effect on us. This brings me onto reovirus, a double stranded RNA virus which is ubiquitous amongst the human population. Many individuals will carry reovirus in their airways and lungs or gut and be completely healthy; the name reovirus itself eludes to this fact being that 'reo' is an acronym of respiratory, enteric, orphan (with orphan denoting that there was no known diseases when the virus was discovered). Some reovirus strains have now been found to cause an infection but it is characterised only by mild flu-like symptoms which people recover from in a short period of time.

The reason behind the lack of disease caused by reoviruses comes from the fact that they do not grow well in normal human cells; however cancer cells are far from normal. As I’ve mentioned, cancers are caused by mutations in normal cells. A defining characteristic of cancerous cells is their ability to grow and divide much faster than their normal counterparts, a change which is controlled by mutation. One of the most common ways this increase in growth speed is achieved is through mutations to a cellular process known as the Ras pathway. When the Ras pathway is mutated the cell goes into overdrive and will grow and divide much faster than its normal counterparts, making it able to form a mass of cells (a tumour). Interestingly, while reovirus grows poorly in normal cells, it is very good at growing in cells that have a mutation in the Ras pathway (though we do not fully understand why). In cells containing the Ras mutation, any infecting reovirus will grow rapidly and cause the cell to lyse (a fancy word for burst), thus killing the cell. This bursting kills the cancerous cell but leaves normal cells perfectly healthy. The bursting of the cancer cells also has an additional advantage in that it can cause activation of the immune system to attack any remaining cancerous cells. The virus and the immune system are therefore able to work in harmony to attack, and kill, the cancer.

Reovirus is capable of infecting, and killing, any cancerous cell that contains a Ras mutation. Ras mutations occur in around 20-30% of all cancers ranging from breast, to prostate, to brain, and so on. Ras mutations can also be seen at levels of up to 90% in some specific cancers (such as pancreatic), so reovirus has the potential to impact a very large number of cancer cases.

The use of reovirus for the treatment of cancer is not just at the idea stage. Oncolytic Biotech® has been working on their product REOLYSIN® for some time now. The product has entered phase III clinical trials (the final step before becoming licensed) as treatment against head and neck cancer and is in phase II trials for other forms of cancer. So far the results are highly promising, the virus is well tolerated and has, at worst, only causes some mild flu-like symptoms. It may not be long before we see REOLYSIN® hit the hospitals as a treatment against head and neck cancer, and potentially other forms as well.

Recent work has also shown that reovirus treatments can be administered into the blood of patients instead of being directly injected to the cancer as was the case with the original procedure. It was believed that if the virus was given in the blood it would simply be destroyed by the immune system, like many other viruses. Instead, it was found that the virus is capable of becoming a stow-away in red blood cells. The virus can enter red blood cells where it is hidden and protected from the effects of the immune system, it then simply waits inside its little red bus until it reaches the cancer stop, where it alights and begins its attack on the cancer cells. Since it is much easier to inject someone in a blood vessel than directly into a tumour, this finding is likely to make reovirus an even more viable option as an anticancer therapy.

The idea of using a virus to treat disease is something I find truly fascinating. Viruses so often get a bad reputation for the damage they have caused, but through continued scientific research we are starting to find ways to turn these old adversaries to our allies. It may not be long before we see reovirus being prescribed as a treatment against cancer.

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