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Oxford researcher secures funding for powerful imaging technique in pancreatic cancer

Pancreatic Cancer Research Fund (PCRF) is funding six new research projects with a total of £1 million – bringing the charity’s support for research into the UK’s most lethal cancer to over £8 million. This is the third year that PCRF has invested £1 million in a single funding round. In total, the charity has funded 40 cutting edge research projects across the UK and Ireland, worth over £6 million.

Oxford researcher Dr Bart Cornelissen will be leading one of the six newly funded projects. Dr Cornelissen aims to use powerful imaging techniques to diagnose early stage pancreatic cancer. His team has already developed an imaging agent that attaches to a protein known as claudin-4 which is expressed in the early stages of the disease. This project will develop the agent so that this protein can be rapidly detected and monitored using PET scanners, which are increasingly common in hospitals. Dr Cornelissen is part of the Cancer Research UK Oxford Centre Pancreatic Cancer working group, and the early stages of this project were supported by an Oxford Centre Development Fund award.

Projects at Imperial College London, University of Liverpool, Swansea University, Cancer Research UK Manchester Institute and Queen Mary University of London, will also receive funding.

These new grants are in addition to the £2 million committed to the Pancreatic Cancer Research Fund Tissue Bank, which launched in January 2016 and will accelerate research progress. The Tissue Bank is the world’s first nationally co-ordinated pancreas tissue bank and has already been hailed as “one of the most important developments in resourcing UK pancreatic cancer research in a generation”.

Says PCRF’s founder and CEO, Maggie Blanks: “In the charity’s early years, we had to focus on basic research to help understand pancreatic cancer and its mechanisms, with the knowledge that this would be a springboard for future research progress. More recently – typified by this year’s grants – we’ve been able to focus on projects that are closer to patients. These include innovative ways of making current treatments much more effective, developing ‘personalised medicine’ approaches and finding ways to diagnose the disease in its earliest stages.

“We’re committed to beating this disease and thanks to our loyal supporters whose fundraising enables us to fund all these projects and initiatives, we’re making real progress towards this goal.”

Genetic expression ‘predicts lung cancer survival’

A study led by Oxford University researchers and colleagues at the National Cancer Institute, Milan, Italy has shed light on a key puzzle thrown up in some lung cancer screening programmes.

Italian researchers have screened more than 5000 heavy smokers over the last fifteen years, using CT scans to detect lung cancer early. While the proactive CT screening of smokers has been good at discovering developing cancer tumours, finding them more frequently than expected, the programmes have not had a clear effect on reducing deaths from cancer. The research team decided to look at whether the way different genes were expressed in various tumours could account for why some people survived and others did not, despite the early detection by the screening program.

Lead researcher Dr Jiangting Hu said: ‘If you are doing well at finding tumours, you would expect to be reducing deaths by treating people earlier. But there was no clear link between this early detection and survival rates. We hypothesised that the screening programmes were mostly finding indolent – slow-growing – tumours. These indolent tumours were removed, but there were also aggressive, fast-growing, tumours developing. These fast-growing tumours do get found by screening but later as they develop and, even if detected very early, already have a very aggressive phenotype.

The researchers looked at the gene expression pattern of tumours that had been detected by CT scans and compared the differences between the pattern detected at baseline and the pattern detected later on. Different expression of some genes can lead similar tumours to behave in different ways. The genetic expression in the tumours was compared with other information about the cancer cases.

The team found 239 genes whose expression was related to cancer survival rates.

Professor of Tumour Pathology and CRUK Oxford Centre Member Francesco Pezzella said:The striking thing was that the 239-gene signature divided the patients into two groups that clearly predicted disease-free survival and also divided the indolent tumours detected at baseline from the tumours which were found later on during the screening program, regardless of tumour stage or size, and any histopathology findings from studying the tissue. We also found that the genetic expression in healthy cells differed between those two groups of people. Furthermore the same signature could divide indolent from very aggressive tumours in patients as part of normal clinical practice.

‘The results confirmed that there is a difference between indolent and aggressive tumours, which could be used to identify those with more dangerous tumours for personalised care. They also show that we could profile healthy tissue to identify high and low risk groups. A final remarkable finding is that the team led by Ugo Pastorino and Gabriella Sozzi in italy has discovered that the same genetic differences can be seen with a blood test in the same patients.

‘The next step will be finding shorter gene signatures, enabling us to develop more personalised diagnosis to facilitate better targeted cancer treatment.’

The paper, Gene Signatures Stratify Computed Tomography Screening Detected Lung Cancer in High-risk Populations, is published in EBioMedicine.

 

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.