Cancers are often resistant to chemotherapy. New drugs and novel approaches to finding those drugs are needed in the ongoing battle against one of the UK’s biggest killers. Dan Richards talks to NC3Rs David Sainsbury Fellow, Dr Adrian Biddle, Queen Mary, University of London, who is working on a new non-animal in vitro method for the development of drugs to target cancer stem cells. Dr Biddle talks about life as a fellow and his hopes for faster progress in the development of anticancer therapies with an approach that replaces the need for animals.
What attracted you to apply for an NC3Rs David Sainsbury Fellowship?
The fellowship is a great opportunity for early-career scientists to gain their own funding and the independence to pursue their own research ideas. There is not much independent funding available for early-career scientists, so I think the NC3Rs fellowship is a really significant new scheme.
I felt that my work was a good fit for the NC3Rs, as I work in a field where there is a lot of ongoing contention over whether investigations are best pursued in vivo or in vitro, and therefore work with a 3Rs focus has the potential to have a big impact in the field. I hoped to use the fellowship to develop my own independent research direction based on a non-animal model for therapeutic targeting of cancer stem cells.
What research are you undertaking with your fellowship funding?
My postdoctoral research in the Blizard Institute at Queen Mary, University of London has focused on the role of cancer stem cells in oral cancer. Cancer stem cells were initially hypothesised to be a small subset of cells within a tumour that had the special ability to keep growing forever, so were essential to the survival of the tumour. The possibility of wiping out the tumour by targeting just a small group of cells has led to intense interest in this theory over the last 15 years.
In the past five years the field has moved forward very quickly. The picture is now more complex, with the process of epithelial-to-mesenchymal transition (where stationary tumour cells change to become more mobile, allowing the tumour to spread) now demonstrated to be a very important cancer stem cell characteristic. My research in oral cancer has found that both the stationary and mobile forms of cancer stem cells show resistance to chemotherapy drugs, so new drugs are needed.
Other researchers have also shown similar therapeutic resistance of cancer stem cells in other tumour types. This is a major problem for cancer therapy, as cells that survive the initial therapy can then drive tumour regrowth and metastasis to distant organs, which is the main cause of death from cancer.
My NC3Rs-funded research now focuses on the development of new non-animal in vitro techniques for identifying drugs that target these cancer stem cells, with the eventual aim of developing therapies that can eradicate the whole tumour.
So how are you using 3Rs principles to drive your research?
In the worldwide scientific community, there is currently great interest and investment in research to find drugs that can target cancer stem cells, especially now cancer is the leading cause of death in the UK and many other countries. Unfortunately, there is a widely held belief that this can only be achieved using in vivo mouse xenograft models. If this in vivo work can be shown to be unnecessary, then this should drive a reduction in the use of mice in cancer stem cell research, and this is the aim of my research.
Are there advantages to using non-animal models for this type of research?
Yes, in vitro models have the advantages of being much cheaper and quicker, and experimental conditions can be closely controlled, including control of environmental factors (such as oxygen concentration and growth factors). Also, due to the ease of visualising individual cells at all time points during the experiment, a much greater amount of information can be obtained from in vitro experiments.
There is therefore a range of benefits from applying 3Rs principles to cancer stem cell research, and this will hopefully drive faster progress across industry and academia in the search for anticancer therapies.
How has the fellowship experience been so far?
So far the experience has been very rewarding. The fact that I have a supportive institute, and my postdoctoral supervisor as a mentor for my independent research, has made the transition much easier than it might otherwise have been, and much more productive! The high profile of the NC3Rs, and the work they do to communicate their science, has brought my work to a much wider audience, which is very satisfying.