Developing new models for prevention or treatment of cancer v1
Development and Application of Ex Vivo Assays to Assess Efficacy Biomarkers in the Prevention and Treatment of Cancer
University of Leicester
Duration of Study in the UK
2 years, 11 months, 31 days
Summary of Research
The results of treatment for advanced cancer remain disappointing despite several advances that have been made over the last 10-20 years. The field of cancer prevention (chemoprevention) uses low toxicity drugs which may help to prevent, delay or reverse the development of cancer, particularly in high risk populations. The ultimate aim for chemoprevention strategies is to reduce the cancer burden in the population and thereby significantly reduce the cost and toxicity associated with treating advanced disease.
Development of chemopreventive and therapeutic agents is significantly hampered by the lack of suitable models which can be used to identify the most promising agents to take forward into clinical trials. Much of the work investigating potential drugs, is undertaken using established cell lines which bear little resemblance to the tumour, which consists of lots of different types of cells that all interact with each other. These interactions are recognised to play an essential role in how a tumour grows, and also in how it responds to treatment.
This study will use excess tissue derived from patients who are undergoing surgery for cancer, a pre-cancerous condition, or a condition which may increase cancer risk. In addition, a blood sample will be taken, in order that we can test whether markers present in the tissue may also be seen in blood.
We will create more relevant model systems that will allow better representation of tissue architecture, in order that the effects of potential preventive and therapeutic drugs can be investigated. This will include use of very thin tissue slices in drug 'baths', sorting of cellular components to analyse effects of drugs on different cell types within a tumour, injection of tumour cells into immunocompromised mice and growth of 3-dimensional cell structures. Furthermore, we will assess potential tumour markers and DNA mutations detected in blood samples
Summary of Research
A system was developed to keep pieces of tumour tissue alive outside of the body (called explants). These explants could then be treated with different chemicals that may treat or prevent cancer.
It was found that when explants were treated with a particular chemotherapy drug, the response was the same as for patients receiving that particular cancer treatment in the clinic. This is really exciting as it means that we can mirror what a drug is doing to the body in a laboratory model. Therefore, we can look more carefully at different parts of the tumour (such as DNA, proteins, immune cells) to understand how treatments work and how patients may respond.
Researchers also found that curcumin, from the spice turmeric, affected a protein (called nanog) in the cells of pre-cancers (bowel polyps). This protein has an important role in pre-cancer cells becoming cancerous, so stopping it from working could be useful in cancer prevention.
A lot more work is now being done to use explants to look at new therapies which target the immune system to help it recognise and destroy cancer cells. It is usually very difficult to research this area in the laboratory as immune cells interact with lots of other cells. The explant system means that we can have a more accurate record of how drugs work on these immune cells.
A number of research papers have been published as a result of this study:
We would like to thank all of the patients at the University Hospitals of Leicester who made this research possible.
Wales REC 4
Date of REC Opinion
23 Oct 2014
Further Information Favourable Opinion