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One drug, multiple uses – how liver disease research might have uncovered a useful cancer treatment

Sometimes discoveries from research into one disease hold promise for many others. This is the case of a new paper published today in the journal Scientific Reports. The team, led by researchers at the IDIBAPS Biomedical Research Institute (Barcelona, Spain) and supported by funding from Worldwide Cancer Research, have uncovered a new therapeutic strategy for liver disease that could also be used to treat a wide range of diseases, including obesity and cancer.

The treatment is based on using small DNA-like molecules, called siRNAs, which can be designed to target and suppress the production of specific proteins. In particular, this new research describes how the team (in collaboration with the company Silence Therapeutics) have produced siRNAs to stop a protein being made that allows the development of abnormal blood vessels associated with cirrhosis and chronic liver disease.

Liver cirrhosis involves damage to the liver characterised by the accumulation of scar tissue, which alters the normal structure and function of the organ, and can ultimately lead to cancer. The accumulation of scar tissue impedes blood circulation in the liver, thus leading to portal hypertension (high blood pressure in the portal vein).

To relieve the pressure, collateral blood vessels develop outside the liver. The problem is that the collateral vessels divert blood away from the liver, which can cause further damage to the organ. Collateral blood vessels can also form varicose veins (swollen or enlarged veins) in the oesophagus and stomach of patients with cirrhosis. These vessels are fragile and have a high tendency to burst, causing heavy bleeding that is difficult to stop.

The formation of new blood vessels – a biological process known as angiogenesis – is also crucial for tumour growth and the spread of cancer to other parts of the body. The researchers believe that this link suggests their proposed strategy could also have a part to play as a cancer treatment.

Dr Mercedes Fernandez, lead researcher at the IDIBAPS Biomedical Research Institute, said: “We used mice with portal hypertension to show that treatment with our specially designed siRNA molecule markedly reduces the development of collateral vessels and impairs the angiogenic potential of cells lining the blood vessels. This suggests that our treatment could be a promising therapeutic strategy for portal hypertension and potentially also for preventing new blood vessels from forming in and around tumours.”

The siRNA used in this research is designed to stop a protein called VEGFR-2 (vascular endothelial growth factor receptor type 2) from being made by cells that line the inside of blood vessels. VEGFR-2 tells the cell to form new blood vessels and has been widely studied in cancer as a target for preventing progression of the disease. However, advances in our understanding of the basic biology have not been matched by advances in treating patients. Dr Fernandez believes that their research could narrow that gap:

“siRNA technology has emerged as one of the most promising platforms for therapeutic product development. Our research team has also developed a related siRNA therapy that is currently being tested in several clinical trials in patients with advanced solid tumours, further supporting the translational relevance and therapeutic potential of this approach”.

As with all research conducted in animal models, we still don’t know for sure whether the same effect will be seen in humans. But these incremental advances give us insight into how these new treatments work and also indicate what might be worth pursuing for drug development. The fact that this therapy may be useful for treating a variety of conditions is really exciting and we will be following the team’s research with interest to see how it progresses.

The full research article can be read for free online here: https://www.nature.com/articles/s41598-017-14818-7

Image credit:  Antonino Paolo Di Giovanna, Wikimedia

Science Communications Manager

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