John Findlay wins Royal Society of Medicine Glaxo Travelling Fellowship

The CRUK Oxford Centre is delighted to announce that The Royal Society of Medicine recently awarded Centre member, John Findlay, its 2014 Glaxo Travelling Fellowship. John is a General Surgery Registrar in the Oxford Deanery, and a Senior Clinical Research Fellow in OesophagoGastric Surgery at the NIHR Oxford Biomedical Research Centre. His research interests focus on personalising therapy for patients with oesophageal and gastric cancer, on the basis of molecular, clinical and radiological biomarkers.

The 2014 Glaxo Travelling Fellowship was awarded for his paper ‘Novel classifications of oesophageal cancer FDG-avid nodal stage and metabolic response to neoadjuvant chemotherapy, and predicting progression to metastatic and unresectable disease’. This paper also won the 2014 Royal Society of Medicine Sylvia Lawler Clinical Poster Prize, and 2014 Association of Upper Gastrointestinal Surgeons of Greater Britain Poster Prize.

This study of 383 patients with oesophageal cancer treated in Oxford at the Churchill Hospital aimed to determine the utility of restaging oesophageal cancer after neoadjuvant chemotherapy with positron emission tomography-computed tomography (PET-CT), and was undertaken as part of John’s PhD. PET-CT was shown for the first time to be twice as sensitive as CT for detecting interval metastases after neoadjuvant chemotherapy for oesophageal cancer, with decision theory supporting routine re-staging PET-CT for all patients. In addition, new classifications of FDG-avid nodal stage and metabolic response to chemotherapy and predictive models were developed, which could identify patients at high risk of interval progression to metastatic or unresectable disease before surgery, and also those with a worse prognosis afterwards.

After his success with this paper John is now exploring whether PET-CT may have a similar predictive role in gastric and other gastrointestinal cancers. He commented that he was honoured to receive this prize on behalf of his collaborators, and hopes very much that these findings will have immediate use in counselling patients with oesophageal cancer, and also in identifying those patients who will benefit from additional staging and re-staging investigations.

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.

New MRI method promising for detecting tiny brain tumours

A new imaging technique may be able to detect cancers that have spread to the brain while they are still small

The Oxford University study, carried out in mice, investigated a new ‘dye’ that shows up in MRI scans.

The scientists showed that the dye, or contrast agent, they have developed recognises and sticks to a molecule called VCAM-1. This molecule is present in large amounts on blood vessels associated with cancer that has spread to the brain from other parts of the body.

MRI scans show the distribution of the dye in the brain, enabling much smaller tumours to be detected than can be done using current techniques.

Cancer that has spread to the brain is extremely difficult to treat successfully.

Small tumours can be treated with whole brain radiotherapy or surgery, and there are new chemotherapy treatments in development. But currently, it is only possible to detect larger secondary brain tumours, and these are more difficult to treat.

Lead researcher Dr Nicola Sibson of the Gray Institute for Radiation Oncology and Biology at the University of Oxford said: ‘We urgently need to find ways to diagnose these cancers at an earlier stage to improve survival rates.  Our research suggests a new possible approach to do just this. The next stage is to build on these results and carry out clinical trials. If successful, we hope that early detection using this technique could increase the number of available treatment options for these patients.’

The research was funded by Cancer Research UK and the Wellcome Trust, with support from the National Institute for Health Research-funded Oxford Biomedical Research Centre.

Dr Julie Sharp, Cancer Research UK’s senior science information manager, said: ‘This exciting discovery reveals that a single protein could enable doctors to literally paint a picture with a medical dye to detect cancer that has spread to the brain, at a very early stage, when treatment has a greater chance of being successful.’

Miracle technique cures grandfather of cancer

A grandfather given “a death sentence” after being diagnosed with advanced bowel cancer has been cured of the disease thanks to a pioneering new technique.

The therapy used on Brian Brooks, 72, involved directly delivering high doses of radiation to tumours deep in the body, via tiny radioactive resin beads injected into his bloodstream. The treatment itself lasted just two days.

Last September doctors told Mr Brooks, a retired dog kennel owner, that he was unlikely to live more than a year after being diagnosed with bowel cancer that had spread to his liver.

However, he was later put on the Foxfire trial, which is testing the new method, called radioembolisation.

Advanced bowel cancer often spreads to the liver, because lots of blood passes directly between these organs.

The size and location of subsequent tumours sometimes makes it difficult to remove them surgically, or treat them using conventional radiotherapy.

This new technique overcomes the the problem by delivering high-dose but short-lived radiation directly into the liver tumours using radioactive ‘microspheres’ injected into their blood supply.

These become trapped in the tumour, killing cancer cells with minimal damage to healthy tissue.

Mr Brooks, from Ely near Cambridge, said: “I was given a death sentence, it’s a very difficult thing to get your head around.

“My family were devastated and one of the worst things for me was thinking I may not see my three-year-old grandson William grow up.”

But he said his wife Nicky, 67, son Iain, 45 and daughter Joanne, 40, “never gave up hope”.

He went on: “To be told you have 12 months to live and then to have completely healed 12 months down the line, we believe, is a miracle.”

His wife added: “We’ve just had the results back and the doctors can’t believe its success – they are astonished.”

Mr Brooks underwent the Foxfire treatment at Addenbrooke’s Hospital in Cambridge over two days last November.

On the first day doctors mapped the blood flow over his liver, and the next day they injected the radioactive microspheres into the tumours’ blood supply.

Four months later he was told the liver tumours had disappeared, and he could commence chemotherapy to shrink the colon tumour. Seven weeks ago doctors removed them.

Mr Brooks said: “Obviously there is always the risk that the cancer can come back but I am now in remission and that is something that the doctors did not believe was possible.”

He is one of about 40 patients in Britain to receive the treatment as part of the trial, supported by Cancer Research UK’s Bobby Moore Fund and co-ordinated by Dr Ricky Sharma of the Gray Institute for Radiation Oncology and Biology at Oxford University.

It tests using radioembolisation plus chemotherapy versus chemotherapy alone, to see if the new method improves survival.

The trial only started 18 months ago and no official results have been reported yet. Dr Sharma hopes to recruit 500 suitable patients from across Britain.

Kate Law, Cancer Research UK’s director of clinical trials said: “Without clinical trials like Foxfire, we wouldn’t be able to improve techniques for cancer that are hard to treat.

“It’s a promising trial and we look forward to following its progress and seeing the results.”

Source: The Telegraph, By