A way of switching off the development and growth of certain cancer cells has been identified by scientists at ProXara Biotechnology Limited, a spin out company from the University of Bristol, UK.
Results to date have proved so positive that the team now plans to develop the drug compound to a point at which it would be close to entering clinical trials, using funding of £2.8 million from the Wellcome Trust's Seeding Drug Discovery initiative.
The ability of cells to commit suicide, or apoptosis, is an important and normal process in the body's development. All cells contain an enzyme called protein kinase B (PKB) which, when activated, triggers a signal that prevents apoptosis.
Certain types of genetic damage, common to many cancer cells, lead to the movement of PKB from the interior of the cell to its surface membrane. When this happens, PKB becomes active, halting apoptosis. Professor Tavaré, lead scientist at ProXara, believes that by preventing PKB binding to the cell’s membrane he can ensure that apoptosis continues, thereby driving the cancer cells to commit suicide and preventing them from forming tumours.
"There has been a lot of interest in targeting PKB as a way of preventing tumour growth," says Professor Tavaré. "Most of the interest so far has been in developing drugs that block the signal which prevents apoptosis. However, such drugs are very non-specific and can have many adverse side effects. We are working on a novel approach to prevent PKB actually binding to the cell membrane."
Professor Tavaré and his team have discovered a drug-like compound, which prevents PKB binding to the cell membrane and makes the tumour cells commit suicide. They now wish to develop this compound to a point at which it would be close to entering clinical trials.
"Professor Tavaré’s research offers a novel approach to cancer drug research," says Dr Ted Bianco, Director of Technology Transfer at the Wellcome Trust, which is funding the research under its Seeding Drug Discover initiative. "Cancer affects one in three people but is a very complex disease to tackle and as a result many anti-cancer drugs have unpleasant side effects. This work has the potential to provide a much more targeted drug with fewer side effects."
Professor Tavaré says that the drug would be used initially to target lung cancer, the second most common cancer in the UK. Almost 38,000 people are diagnosed with this particular cancer each year. If the approach works, it could be adapted to treat other types of cancer or even inflammatory diseases such as arthritis or asthma.
"We anticipate that a drug based on this approach could work in up to half of people with lung cancer," explains Professor Tavaré. "As well as developing the drug itself, we are also working on a way of identifying which individuals are most likely to respond to the drug."
This targeted therapy is based on five years of research by Professor Tavaré and Dr Paul England at ProXara Biotechnology Limited, a spin-out company from the University of Bristol. Following intense competition from 86 other universities and companies, the research has now been given a major boost of £2.8 million under the Wellcome Trust's Seeding Drug Discovery initiative. Only three projects were funded under this scheme.
The initiative aims to bridge the funding gap for health researchers involved in early-stage drug discovery projects that will be the springboard for further research and development by the biotech and pharmaceutical industry.