Metal test could help diagnose breast cancer early

A team, led by Oxford University scientists, took techniques normally used to analyse trace metal isotopes for studying climate change and planetary formation and applied them to how the human body processes metals.

In a world-first the researchers were able to show that changes in the isotopic composition of zinc, which can be detected in a person’s breast tissue, could make it possible to identify a ‘biomarker’ (a measurable indicator) of early breast cancer.

A report of the research by the Oxford University-led team, which included researchers from Imperial College London and the Natural History Museum, London, is published in the Royal Society of Chemistry journal Metallomics.

The pilot study analysed zinc in the blood and blood serum of ten subjects (five breast cancer patients and five healthy controls) alongside a range of breast tissue samples from breast cancer patients. By using techniques that are over 100 times more sensitive to changes in the isotopic composition of metals than anything currently used by clinicians, the researchers were able to show that they could detect key differences in zinc caused when cancer subtly alters the way that cells process the metal. Similar changes in copper in one of the breast cancer patients is additional evidence that it may be possible to identify a biomarker for early breast cancer that could form the basis of a simple, non-invasive, diagnostic blood test.

‘It has been known for over a decade that breast cancer tissues contain high concentrations of zinc but the exact molecular mechanisms that might cause this have remained a mystery,’ said Dr Fiona Larner of Oxford University’s Department of Earth Sciences & CRUK Oxford Centre Member, who led the research. ‘Our work shows that techniques commonly used in earth sciences can help us to understand not only how zinc is used by tumour cells but also how breast cancer can lead to changes in zinc in an individual’s blood – holding out the promise of an easily-detectable biomarker of early breast cancer.’

The researchers say that this new understanding of cancer cell behaviour – in particular the role sulfur-containing proteins play in how tumours process zinc – could also help in the development of new cancer treatments.

‘The hope is that this research is the beginning of a whole new approach,’ said Dr Larner. ‘Understanding how different cancers alter different trace metals within the body could enable us to develop both new diagnostic tools and new treatments that could lead to a ‘two-pronged’ attack on many cancers. Further research is already underway to see what changes in other metals may be caused by other cancers.’

A report of the research, entitled ‘Zinc isotopic compositions of breast cancer tissue’, is published in the journal Metallomics.

Professor Gillies McKenna awarded the Gold Medal by the Royal College of Radiologists

In recognition of the outstanding contribution that he has made to the field of radiation oncology, CRUK Oxford Centre Director, Professor Gillies McKenna, has been awarded the Gold Medal by the Royal College of Radiologists. He also delivered the twelfth David Skeggs lecture, titled Imaging and Targets: The Molecular Frontiers in Radiation Oncology.

The Gold Medal is the most prestigious honour awarded by the Council upon the recommendation of the Honours Committee. Previous winners include Professor Peter Hoskin, Professor Dame Janet Husband DBE and Professor John Mallard. A full list of winners is available here.

Professor McKenna commented: “There is no higher honour that any clinician or scientist can receive than to be recognised by their peers. I recognise too that this is an acknowledgment that in the last ten years we have together brought back British radiation oncology and radiation biology research from a point where we wondered if it was going to survive as a discipline, to the point where we can proudly hold our heads high once more as world leaders. It has been a great privilege to me to have contributed to this revival, and I gratefully acknowledge the support I have received from the Royal College and its members in my work.”

 

Image reproduced with permission of The Royal College of Radiologists. Copyright Ede and Ravenscroft and RCR.

Reverse the Odds – Nominet Trust 100 Winner

Nominet Trust proudly announced that Reverse The Odds, an app that is helping CRUK Oxford Centre member Dr Anne Kiltie identify biomarkers in tumour samples, has been named among the 2014 Nominet Trust 100 (NT100) – a global list of 100 inspiring ventures from around the world.

Projects featured on the list are using technology to tackle some of the world’s biggest social problems from education and human rights abuses to climate change and health. Following a global call for nominations earlier this year Reverse the Odds has been selected by an independent steering committee in recognition of its fantastic game design, data analysis expertise and remarkable production that come together to allow citizen scientists to fight cancer. Reverse the Odds is the third Citizen Science project and has already analysed 2 million tumour samples. The game can still be played, visit the website to download the app and join in.

Commenting on their inclusion in the NT100, Dr Anne Kiltie said: “The app lets members of the public score our immunohistochemistry images for us. The public have already looked at one protein and we are about to compare the public’s scores with our ‘expert scores’ to see how well they match. There are other images in the app which are being analysed for a group in Southampton and their results are being compared at present, so the result is imminent”.

Annika Small, CEO of Nominet Trust, the UK’s leading tech for good funder, said: “There is a striking progression in the quality and maturity of this year’s NT100, indicative of a wider evolution in the ‘tech for social good’ sector as a whole. More people than ever before are using technology to solve problems that matter to them in bold new ways. This year’s NT100 list is populated by extraordinary people with inspirational stories to tell and it shows us that imagination, social conscience and technology make a potent mix to affect change.”

To see more about Reverse the Odds and the other Nominet Trust 100 winners visit the website.

 

Scientists Discover Why Bowel Cancer Sometimes Outsmarts Treatment

A new study that challenges the prevailing view of how bowel cancer develops in the large intestine is published today in Nature Medicine.

Cancer Research UK scientists have discovered that bowel cancer may not be restricted to starting its journey in the stem cells in the lining of the intestines as previously thought.

The researchers, based in Oxford at the Welcome Trust Centre for Human Genetics, studied a hereditary faulty gene which can cause bowel cancer in middle age. The faulty gene causes normal cells to behave like immortal stem cells and develop tumours of their own– challenging the theory that normal cells have a fixed fate and limited lifespan.

The cells lining the bowel are continuously replaced – new ‘daughter’ cells are produced by immortal stem cells to replace those that have worn out.

Many types of cancer are caused when chemical messaging goes wrong. Scientists analysed polyp samples from hereditary bowel cancer patients and found disruption of a key signalling pathway involved in stem cell control. They found the same problem in a wider selection of bowel cancer tumours. When they altered the key signalling molecule in the lab it caused daughter cells that had moved out of the stem cell zone to behave like stem cells and develop into tumours.

This could ultimately explain how some cancers become resistant to chemotherapy, as stem cells killed by the treatment may be continually replaced by cancerous daughter cells.

Simon Leedham, CRUK funded researcher at the Welcome Trust Centre for Human Genetics and CRUK Oxford Centre member, said: “This study has implications for drug development and tumour treatment. If these signalling pathways are disrupted in tumours then daughter cells could revert back to behaving like stem cells and then replace any cancer stem cells killed by chemotherapy”

“This may be one of the mechanisms behind tumour resistance to chemotherapy but could also represent a potential drug target. If we can restore the disrupted signalling balance in tumours then we may be able to stop daughter cells from replacing cancer causing stem cells and increase the effectiveness of our current therapies. ”

Professor Tim Maughan, Professor of Clinical Oncology and CRUK Oxford Centre Networking Lead, commented: “This new insight into the way bowel cancer develops is critically important. People with the type of cancer described may respond to different types of therapy and we can now test that in our sample sets from previous patients. Understanding the mechanism will help us design new approaches to treating this subgroup of patients to improve their outcome”

Read the more about the study, Aberrant epithelial GREM1 expression initiates colonic tumourigenesis from cells outside the crypt base stem cell niche, Davis et Al, here.