Understanding the building blocks of cancer gives vital clues to treatment

Research into the cellular and molecular basis of cancer has discovered how controlling the protein activity in cells could help treat colorectal cancer.

Improving survival rates for colorectal (bowel) cancer, and the lives of patients, is one of the key driving factors for biomedical scientists at Bristol University whose research lays the fundamental building blocks for clinical application.

Professor Ann Williams, a member of Bristol’s Cancer Biology Group, has been investigating colorectal cancer for 25 years, examining both the known and unknown contributors to the disease to identify new targets for the prevention and treatment of colorectal cancer.

While survivor rates are improving, Professor Williams emphasises that between 50 to 80 per cent of colorectal cancers are preventable, and that chemoprevention (primary and secondary), provides one of the greatest opportunities to impact significantly on a disease that remains the fourth most common cancer worldwide.

Funded by Cancer Research UK, the group’s primary focus is to unpick the biological make-up of colorectal cancer, to understand what exactly triggers normal cells to transform into cancer cells. By identifying which pathways are important, Professor Williams aims to define which pathways to target with intervention therapies for the better treatment and prevention of the disease.

The laboratory’s research is conducted using human colorectal models, a specialism that the group in the School of Cellular and Molecular Medicine is well known for. Findings are then validated in patient models through the laboratory’s partnership with Bristol’s hospitals, giving the work an exceptional level of credibility.

Examining the link between inflammation and bowel cancer

Professor Williams and colleagues are particularly interested in the link between inflammation and cancer due to the knowledge that people with chronic inflammatory bowel disease have a higher risk of developing colorectal cancer.

The use of human and patient models was a pivotal approach in identifying the protein BAG-1 as a co-factor of the NF-kB signalling pathway, having found that BAG-1 was highly expressed in colorectal cancer tissue.

Professor Williams’ laboratory is now exploring the potential pro-cancerous function of such regulators of NF-kB activity, and their role in promoting tumour cell survival.

In inflammatory bowel disease, NF-kB activity is stimulated in the epithelial cells. The function of cell specific regulators of NF-kB activity appear to promote epithelial cell survival under inflammatory conditions and therefore increase the potential of these cells to become cancerous.

One regulator of NF-kB that has the tendency to produce tumours is Bcl-3. The lab is therefore concerned with finding out how therapeutic intervention could be engineered to stop Bcl-3 from being induced, which in turn, could stop cells from becoming cancerous.

Could aspirin help prevent cells becoming cancerous?

Excitingly, it appears that Bcl-3 happens to be suppressed by aspirin in tumour cells, which forms the second, complementary strand of Professor Williams’ research – developing a molecular understanding of why and how certain biological determinants help to prevent cancer.

It is known that aspirin prevents the formation of intestinal polyps in animal models, and there is an accepted link between regular aspirin use and a reduced risk of colorectal cancer.

Clinical trials are due to take place in Bristol that will follow patients already taking aspirin to track their progress. The trials will look at a novel use for aspirin in sensitising cells to chemo-radiotherapy, which patients with rectal cancer often undergo prior to surgery.

In collaboration with Professor Chris Paraskeva, Prof Williams hypothesises that those patients who are taking aspirin will respond better to chemo-radiotherapy than those who are not. If that proves to be the case, it would provide the empirical evidence to support the potential use, (pending further investigation), of aspirin to improve the clinical response to conventional therapy.

Their research will make a vital contribution to understanding how to reduce the chances of cancer developing, how to control the disease and improve the prognosis for patients in the advanced stages of colorectal cancer.

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