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Research into potential new combination therapy shows promise

Posted by: Research 30 September 2015

Researchers from Stanford University School of Medicine have published encouraging results of their work that aims to develop a new combination therapy for pancreatic cancer. The research, published last week in Nature Medicine, reported that a new combination of two drugs, a new molecule called JQ1 and existing drug vorinostat, has been shown to block and shrink the growth of pancreatic tumour cells. 

There remains a lot of uncertainty about what causes pancreatic cancer and researchers around the world are undertaking vital work to investigate the causes of the disease and the risk factors associated with it. Previous research has shown that the disease can be caused by a mutation in a particular gene called ‘KRAS’, which produces proteins that are vital for many of the body’s functions. In the past, researchers have focused work on drugs that act to target the proteins produced by the mutated KRAS gene, but these drugs have often resulted in severe side effects. This piece of research instead focused on drugs that affect the gene itself, rather than the protein, with the aim of avoiding these unwanted side effects.

The research team began by looking at the effect of a new small molecule called ‘JQ1’ on the growth of pancreatic tumour cells in the lab. They found that the drug slowed the growth of the tumour cells and in a further study were also able to significantly shrink the size of the tumour. The new drug was shown to work by inhibiting the expression of a specific gene, i.e. by disabling how the gene could be “read” by cells in the body. Past research has shown an association between this particular gene and pancreatic cancer. Whilst the effects of the drug on the pancreatic cancer cells were encouraging, they were not strong enough to significantly improve overall likelihood of survival.

The team progressed their research by testing JQ1 in combination with eight other drugs to see if an improved effect could be seen. When testing JQ1 with a drug called vorinostat they saw extremely promising results with a marked reduction in tumour size and a significant impact on overall survival time. This combination of drugs also showed no noticeable side effects.

Vorinostat is a drug that has already been approved for difficult-to-treat lymphoma. This sort of approach is known as ‘drug repurposing’, where an established medicine (e.g. one that has been approved by regulatory authorities in one disease or condition) is further investigated for use in treating one or more additional diseases or conditions. This approach is extremely important as the development of new medicines is a costly and lengthy process – the Association of the British Pharmaceutical Industry estimates that it costs approximately £1.15 billion and takes over 12 years to bring a new medicine to patients. Drug repurposing is advantageous because established medicines will have already completed all of the manufacturing, toxicity testing and clinical trials necessary to obtain regulatory approval. This means much of the cost and time associated with the development process can be avoided.

The researchers will now work to understand more about how the combination works on a molecular level, but are hopeful that they could begin testing in the clinic within the next five years.

Leanne Reynolds, Head of Research, Pancreatic Cancer UK, comments, “This is an exciting avenue of research with promising results showing how a drug already used to treat another disease could be repurposed for pancreatic cancer. We welcome research looking into establishing new treatment options which are urgently needed to improve the shocking pancreatic cancer survival rates, which have improved very little in the last 40 years. Further research is needed to take this work forward before we can tell if it will lead to a new treatment, but we will be excited to follow this team’s progress.”