Friday, March 2, 2012

Treatment of brain cancer with viruses underway

Many novel therapies are being developed for the treatment of brain cancer. Tumours of these kind are relatively hard to treat, because they reside in very delicate tissue. Also, there's the issue of getting a specific drug into the brain: the body is working hard to prevent any foreign stuff coming in. A new concept developed by the University of California in San Diego in collaboration with Tocagen Inc. makes use of viruses to treat patients with an aggressive form of brain tumour. It is currently in clinical trials, which means it is not that far from actual clinic use.

Drug delivery
Making use of a virus in drug therapy has several benefits. They often infect specific cell types, which is something scientists can modify. It is therefore possible to create a viral particle, or vector, that infects only cancer cells. And that is exactly what researchers have done. Additionally, viruses have excellent ways to get themselves inside cells and replicate there. Viruses primarily consist of a string of genetic code wrapped in a package. At the University of California, they found a way to get a specific viral vector to deliver its genetic code to tumour cells in glioblastoma patients, the most common and severe form of brain cancer.

After the virus enters the tumour cell, its genetic code is inserted into the genome, where it sits along with the rest. Normally, cells read the DNA to provide them with the required instructions to build proteins. The same happens with viral DNA, which has been sneaked into the genome. Basically, viruses abuse the cellular machinery to propagate their spread throughout the body. Because the scientists only allow it to target cancer cells, it is exactly what we want. Even though an ordinary virus infection is hardly something to get excited about.

Because the custom build virus is loaded with genetic code that provides the blueprint for an anti-cancer drug, the cell is basically digging its own grave. After the viral DNA is read, the tumours creates a drug commonly referred to as 5-FU. After its conception it is processed by the cell into several toxic molecules which are inserted into the genome. In turn, this leads to irreparable damage which forces the cell to kill itself. It is not the first time an anti-cancer therapy forces the cell to kill itself from within: a previous study revealed a novel method which involved a protein switch treating cancer by killing cells from the inside.

Current treatments
Brain cancers are commonly treated with radiation therapy and chemotherapy, both which are not very specific and harm the tissue around the tumour. Especially with tumours that involve the brain, specific therapy is highly required, because damage in this area is highly undesirable. Because 5-FU is also toxic to healthy cells, though in lesser extent, getting a virus to deliver the payload specifically to cancer cells results in much less side effects. In turn, it renders us able to deliver drugs in much higher concentrations.

Cancer therapies specifically targeted towards the tumour are going to provide the next generation cancer drugs, promising less side effects and higher efficacy. Viruses, which are normally out there to harm us, are one of the tools currently being used and investigated. They are already commonly used for genetic modification because of the way they nest in the DNA. Because the method, which the company Tocagen is trying to market, is already in clinical trials, it is especially promising. The outcome is unsure, but its efficacy has already been proven in experimental models. Now, the question is whether we find any real results during clinical use. 

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