Genes carried by E.Coli bacteria linked to colon cancer
Scientists at the University of Liverpool have identified a type of E.coli bacteria that may encourage the development of colon cancer.
The Liverpool team had previously shown that people with colon cancer and with the inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, have high numbers of a sticky type of E.coli in their colons.
The team have now found that E.coli bacteria, which carry pks genes that encode a toxin that damages DNA in the cells of the gut lining, are more commonly found in the colons of patients that have inflammatory bowel disease and colon cancer than those that do not have these conditions. Approximately two thirds of patients with colon cancer carry these E. coli compared with one in five with a healthy colon.
Research, in collaboration with the University of North Carolina, showed that mice with colitis are more likely to carry these E. coli and they often develop colon cancer when carrying E. coli containing pks genes. They did not, however, develop cancer with identical E. coli that did not contain pks. They also found that the presence of E. coli carrying the pks genes did not appear to increase inflammation of the gut.
Professor Jonathan Rhodes, from the University’s Institute of Translational Medicine, said: “The fact that the pks-positive E. coli seemed to promote colon cancer in mice without causing increased inflammation led us to investigate its possible role in human colon cancer.
“The marked increase in the presence of these bacteria in the colon, not only in patients with inflammatory bowel disease, but also in patients with colon cancer who do not have inflammatory bowel disease, suggests that damage caused to DNA, as a result of the toxin that the pks genes produce, may promote the development of colon cancer.”
Dr Barry Campbell, co-author of the research at the University of Liverpool, said: “The research suggests that E. Coli has a much wider involvement in the development of colon cancer than previously thought. It is important to build on these findings to understand why this type of bacteria, containing the pks genes, is present in some people and not others.”
The Liverpool team involved in this study were also the researchers that discovered that dietary agents, particularly plantain and broccoli, could prevent the uptake and transport of E.coli through cells in the gut. They also found that fat emulsifiers in processed food encouraged the movement of bacteria through the cells.
Friday 17 August 2012
Cancer Research UK Press Release
Cancer Research UK’s Drug Development Office (DDO), in collaboration with academia and industry, has announced a new trial to open in Oxford.
The trial will test an experimental drug from AstraZeneca in patients with advanced oesophago-gastric cancer – a disease for which no well-established standard treatments exist.
The Phase I national trial is the second study to open through the Experimental Cancer Medicine Centre (ECMC) Combinations Alliance initiative, which launched last year to run trials of the newest and most exciting combinations of cancer medicine for UK patients.
Cancer Research UK’s DDO is working in partnership with AstraZeneca and the ECMC network to provide strategic oversight and funding to the trial. AstraZeneca is providing the investigational drug AZD8931 and additional funding. Oxford University is sponsoring and managing the trial with support from the Oxford NIHR Biomedical Research Centre.
The trial will investigate whether combining the experimental drug AZD8931 with existing chemotherapy drugs, called oxalipatin and capecitabine, is more effective than treatment with chemotherapy alone.
Survival rates for patients with these cancers remain low, with less than 20 per cent of patients in England surviving for five years. Around 12,600 people in the UK die from these cancers each year.
Chief Investigator, Dr Anne Thomas, a clinical reader in the Department of Cancer Studies and Molecular Medicine at the University of Leicester and consultant oncologist at Leicester Royal Infirmary, said: “It’s wonderful news that this trial is opening, testing a promising new way to treat oesophago-gastric cancer.
“There still isn’t a standard treatment plan for these diseases and patients are often diagnosed at a late stage when there are fewer options available. So there’s an urgent need to innovate, and develop new and effective treatments.
“The opening of this trial brings fresh hope for the future and we’ll follow the results with great interest.”
Dr Ian Walker, head of alliance management at Cancer Research UK’s DDO, said: “We’re delighted to see the Combinations Alliance with AstraZeneca is now opening a second trial – demonstrating the value and importance of such collaborative partnerships. This trial is particularly important as oesophago-gastric cancers remain difficult to treat. It’s clear that without the Combinations Alliance this trial may never have taken place and this is an excellent example of what can be achieved through such collaborations.
“By combining molecularly-targeted experimental drugs developed and owned by the company with other treatments, we’re able to increase the options for patients and, we hope, save more lives in the future.”
AstraZeneca is the first pharmaceutical industry partner to join the initiative. The Combinations Alliance will be expanded to include more partners and establish cross-company agreements, providing patients with access to a larger number of potential combinations.
AZD8931 works by blocking a family of proteins called erbB which are found on the surface of cancer cells in the oesophagus and stomach. The erbB proteins tell cancer cells to carry on dividing. Turning off this signal will help kill the cancer cells.
Graham Richmond, project leader for AZD8931 at AstraZeneca, said: “It is increasingly evident that strategic partnerships such as this are highly valuable in determining the broader utility of new experimental compounds such as AZD8931 for patients with oesophago-gastric cancer. Through collaborations, we are able to explore the potential of combination therapies for cancer, building on our strong oncology heritage and at the same time tapping into external expertise.”
For media enquiries please contact the press office on 020 3469 8300 or, out-of-hours, the duty press officer on 07050 264 059.
Notes to editors
*Fluoropyrimidine-based and platinum-based combinations with or without a third drug (epirubicin or docetaxel) are the most commonly used combinations in Europe and the USA.
The trial will take place at three UK centres: Leicester Royal Infirmary, Churchill Hospital Oxford, and Belfast City Hospital. Professor Mark Middleton, is the lead clinician for the Oxford arm of the trial. Professor Mark Middleton is also funded by the NIHR Oxford Biomedical Research Centre. Dr Martin Eatock is the lead clinician for the Belfast arm of the trial.
The first part of this trial will aim to establish the correct dose of AZD8931 to give in combination with chemotherapy. The second part of the trial will compare those receiving AZD8931 plus chemotherapy, with those receiving chemotherapy alone.
Age-standardised five-year relative survival rate, adults (aged 15-99), England 2005-2009.