Research in the Department: Cancer Biology

With laboratories based both in the School of Medical Sciences and in the Bristol Royal Infirmary, the interests of our group cover a number of aspects of colorectal cancer research including: Epithelial regeneration and mucosal repair, the role of dietary fibres on colorectal cancer, the molecular cross talk between cell adhesion molecules (E-cadherin) and growth factor receptors (EGF receptor). A major interest of my group involves understanding the mechanisms by which cell adhesion molecules can influence signalling pathways in colorectal epithelial cells, as deregulation of these pathways is important in the development of colorectal cancer.

Home page for Professor Massimo Pignatelli

Paediatric oncology is the study and treatment of cancer in children. Approximately 1:650 children develop cancer before the age of 15 years....this makes cancer a much less common diagnosis than seen in adults but this figure is perhaps still more common than many people realise. Approximately 1500 children are diagnosed with cancer each year in the United Kingdom, many of them are very young (about half of them are under the age of seven when they are diagnosed). The types of cancer seen in children are very different to that in adults - about one third have leukaemia (cancer of blood forming cells), one quarter have tumours affecting the brain and the remainder have a variety of, often rare, forms of cancer many of which are only seen in childhood. Fortunately, over the past 20 - 30 years, the results of treatment for many children with cancer have improved dramatically and nowadays we hope to be able to cure about 70% we treat. But treatment is very demanding and can be risky and one of the most important challenges for the future is to understand more about why some children respond well to treatment and others do not. Our work ranges from studies in the laboratory which explore the genetic control of cancer cells in the hope that this will help us identify ways to deliver better forms of treatment, to setting up international studies to explore whether new forms of treatment really can improve cure rates further.

Childhood cancer is fortunately rare, affecting only about 1 in every 600 children, but it remains the commonest cause of death in children after accidents. The CLIC Research Unit was set up in 1985 to study the fundamental changes that cause cancers to develop in children. These changes are defects in the genetic information (DNA), which is divided up into genes, each specifying a particular protein. In cancer there can be alterations in the primary DNA sequence that make genes defective (mutations) or more subtle changes causing too much or too little protein to be made (epigenetic changes). The major project in the Research Unit involves the identification of novel epigenetic defects in childhood cancers, which employs cutting-edge technologies for screening for alterations in thousands of genes simultaneously. The results will provide invaluable information for clinical diagnosis as well as identifying new targets for therapy. One of the very attractive properties of epigenetic changes is that they are potentially reversible, unlike mutations, so studies of epigenetic changes could lead to completely new ways of treating cancer.

Home page for Dr Keith Brown

CLIC Sargent research group

Cells in our bodies have the ability to grow and function in very specialized ways. For example, nerve cells produce proteins which are used to transmit information between the brain and the body, whereas cells in the liver produce proteins often involved in removing toxins from the body. Thus, in normal circumstances, cells are "programmed" to perform certain tasks using the set of proteins they produce.

In cancer cells, however, the normal programming goes awry, with the cells producing too little or too much of certain proteins. The overall effect of such changes is often the uncontrolled cell growth of cancer cells. We at the CLIC Research Unit are investigating how the normal programming of cells goes wrong in cancer cells, and how we may use the detection of such changes in cancer diagnosis and therapy.

Home page for Dr Karim Malik

CLIC Sargent research group

Cancer of the Large Intestine (bowel cancer) is the second most common cause of cancer deaths in the industrialised world. It develops due to mutations in growth control genes such as proto-oncogenes and tumour suppressor genes. About 17,000 people in the UK alone die of bowel cancer every year. It is thought that the high incidence of bowel cancer (and other cancers such as breast and prostate cancer) in the West is due to dietary factors and that between 50-70% of bowel cancers are preventable. Regular intake of aspirin also reduces cancer risk. Our research investigates how certain diets and aspirin reduce the risk of cancer and also how to develop new treatments for cancer. Of particular interest we are examining how to trigger cancer cells to commit cell suicide (through a process called apoptosis) without harming normal healthy cells.

Home page for Professor Chris Paraskeva

The colon is lined with a continually replicating layer of cells (epithelium), which are responsible for nutrient and water absorption as well as mucus production. It is this layer of cells that give rise to colorectal cancers. Disruption of the balance between cell proliferation and cell death can lead to the early stages of cancer. Our research focuses on understanding how cell numbers are regulated in the colon and how deregulation of this process can lead to cancer. The aim of this work is to identify strategies to prevent colorectal cancer and to identify novel molecular targets for the development of effective treatments.

Home page for Dr Ann Williams

Chemoprevention aims to prevent or delay cancer at an early stage before cells become malignant. Chemopreventive agents of particular interest in relation to oral cancer are the retinoids (derived from vitamin A) and inhibitors of the cyclooxygenase 2 enzyme. Apoptosis is a genetically controlled cell suicide pathway that is an important mechanism for eliminating cells during development and in maintaining the correct number of cells in tissues. Apoptosis can be an important mechanism by which chemopreventive agents prevent cancer. It is also the mechanism by which conventional treatments such as radiotherapy and chemotherapy function. Our research aims to understand how the deregulation of apoptotic pathways can contribute to the development of oral cancer and how such defects lead to resistance to chemopreventive agents such as retinoids as well as conventional therapies.

Home page for Dr Angela Hague