New Era in Precision Medicine for Pancreatic Cancer

The development of new treatments for pancreatic cancer is set to be transformed by a network of clinical trials, aiming to find the right trial for the right patient, after a £10 million investment from Cancer Research UK today.

The investment will support the PRECISION Panc project which aims to develop personalised treatments for pancreatic cancer patients, improving the options and outcomes for a disease where survival rates have remained stubbornly low.

A team of researchers from across the UK, including Oxford Centre member Dr Eric O’Neill, aim to speed up recruitment and enrolment of pancreatic cancer patients to clinical trials that are right for the individual patient.

Dr Eric O’Neill said: “the overall goal for PRECISION Panc is to personalise cancer treatment for Pancreatic cancer patients based on their particular genomic background. Oxfords role is to assess whether radiotherapy offers a therapeutic advantage to molecularly targeted approaches for some of the more common pancreatic cancer subtypes. We will be working closely with our partners in PRECISION Panc to ensure findings are expedited into clinical trials to bring advantages to patients as soon as possible”

The researchers will use the molecular profile of each individual cancer to offer patients and their doctor a menu of trials that might benefit them. The first wave of research will establish the best way to collect and profile patient tissue samples. Each patient will have up to five samples taken from their tumour at diagnosis for analysis at the University of Glasgow. The results will guide clinical trial options in the future.

The three trials planned as part of this initiative will recruit a total of 658 patients from a number of centres across the UK – with the scope to add more trials in the future. Patients may also be helped onto suitable clinical trials that are already up and running.

Professor Andrew Biankin, a Cancer Research UK pancreatic cancer expert at the University of Glasgow, said: “PRECISION Panc aims to transform how we treat pancreatic cancer by matching the right treatment to the right patient. Because the disease is so aggressive, patients may receive no treatment at all or if they are given an option it will be for just one line of treatment, so it’s essential that the most suitable treatment is identified quickly. It’s important we offer all patients the opportunity to be part of research alongside their standard care.”

The programme will ensure discoveries from the lab rapidly reach patients, and that data from clinical trials feed back into research of the disease. Cancer Research UK’s investment will support two of the three clinical trials, preclinical work, assay development, biomarker work and the huge amount of molecular sequencing. The charity’s funding will also provide overarching support though project management, funding staff, and a steering committee.

Professor Biankin added: “PRECISION Panc has been developed over the course of three years through the unwavering commitment of pancreatic clinicians and researchers who see that the patients deserve much more than is currently available to them. I’m fully committed to this project and I believe we’re on the cusp of making some incredible advances which will provide therapeutic options to help people affected by this terrible disease. Without Cancer Research UK and their vision for cancer precision medicine, and the commitment of the other stakeholders, we couldn’t get PRECISION Panc up and running.”

Dr Ian Walker, Cancer Research UK’s director of clinical research, said: “This ambitious project marks a new era for pancreatic cancer. Little progress has been made in outcomes for pancreatic cancer patients over the last 40 years, and we believe that PRECISION Panc will reshape how we approach treatment development. Cancer Research UK is determined to streamline research, to find the right clinical trial for all pancreatic cancer patients and to ensure laboratory discoveries have patient benefit.”

Image copyright Dr Eric O’Neill, CRUK / MRC Oxford Institute for Radiation Oncology

Radiotherapy risks are much higher for smokers

Smokers treated for breast cancer have much higher risks than non-smokers of developing lung cancer or heart attack as a result of radiotherapy – according to a new study funded by Cancer Research UK and published in the Journal of Clinical Oncology.

The study shows that for non-smokers the long-term  risk of death from lung cancer or heart attack – caused by radiation – is only  0.5 percent. But for smokers, this increases to around 5 percent.

These findings are based on a worldwide study by the Early Breast Cancer Trialists’ Collaborative Group of the lung and heart radiation doses and risks among 40,781 women with breast cancer in 75 randomised trials of radiotherapy.

Because modern breast cancer radiotherapy techniques have improved and are now better at sparing the lungs and heart than those used in the trials, the researchers also reviewed recent literature so they could take into account how radiotherapy is better targeted today.

Dr Carolyn Taylor, radiation oncologist and lead author from the University of Oxford, said: “For non-smokers, the absolute risk of death from the side effects of modern radiotherapy is only about 0.5 percent, which is much less than the benefit. But for smokers, the risk is about 5 percent, which is comparable with the benefit.

“Stopping smoking at the time of radiotherapy will avoid most of the lung cancer and heart disease risk from radiotherapy, and has many other benefits.“

Radiotherapy remains an important treatment for breast cancer and reduces the likelihood of dying from the disease. For most non-smokers or ex-smokers the benefits of radiotherapy will far outweigh any risks. But for some long-term continuing smokers, the risks may be greater than the benefits.

Dr Julie Sharp, Cancer Research UK’s head of health information, said: “This research highlights that breast cancer patients who smoke need to be offered help and support in order to try and quit to minimise any risks from their treatment. It’s important to remember that modern day radiotherapy techniques have been refined and improved to make sure it is targeted and effective while reducing the risk of side-effects.”

2017 Symposium Registration – Open now!

The day will be a celebration of the wealth of excellence we have here in Oxford, and the passion and commitment to cancer research that is shared across our community.

The 2017 symposium will focus on the themes of Prevent, Detect & Cure, and feature multidisciplinary speakers from across the University and Oxford University Hospitals NHS Foundation Trust.

Confirmed speakers include:

  • Prof Tim MaughanCRUK / MRC Oxford Institute for Radiation Oncology
  • Prof Xin Lu, Ludwig Cancer Research
  • Prof Zhengming Chen, Nuffield Department of Population Health
  • Prof Constantin Coussios & Prof Eleanor Stride, Institute of Biomedical Engineering

The event is exclusive for Cancer Research UK Oxford Centre members, and we look forward to welcoming you to the Saïd Business School on Friday 23rd June 2017.

Oxford Centre members can sign up here

CRUK Science Blog: Training viruses to be cancer killers

For decades, scientists and doctors have looked for ways to stop the damage that viruses cause to humans.

But in recent years, certain safe, modified viruses have emerged as potential allies to tackle cancer.

And our scientists are among those searching for new forms of cancer-killing viruses.

Previous studies have shown that some viruses naturally kill cancer cells, but how they do this has never been fully understood.

Professor Len Seymour’s lab, at the Cancer Research UK Oxford Centre, has been focusing on one particular cancer-killing virus that operates under the code name of Enadenotucirev (or EnAd for short).

And a new study, published in Molecular Therapy – Oncolytics, has revealed EnAd to have a rather unusual method of killing cancer cells.

Arthur Dyer, a researcher in Professor Seymour’s lab, and the team have installed their own version of ‘cell CCTV’ to catch the act of cell-killing on camera.

The footage below was recorded using a normal light cell microscope, commonly found in a lab that takes a snap every minute.

“Each frame is one photo taken every minute and then we’ve stuck all the photos together as a video,” says Dyer. The end result is the clip below:

Dyer explains: “Here we’ve got human lung cancer cells in a dish and we’ve infected them with a virus that’s trained to kill cancer cells.”

This lab technique has given researchers valuable intelligence as to how EnAd kills cancer cells.

“When the cells are infected with the virus they balloon up, blister and then die,” says Dyer, adding that it was a cause of cell death he’d never seen before.

“When I first saw it I thought I was going mad. It’s such a weird cell death, it seems to use up the energy in the cell which then causes it to swell.”

One of the ways in which viruses survive in the human body is by hijacking healthy cells’ internal machinery.

EnAd takes over the cancer cells’ machinery, using up the cell’s energy to such an extent that it has no more strength left to live.

“This virus needs cells that are already hyperactive,” adds Dyer, explaining that as the metabolism of cancer cells has gone haywire they make the perfect victim.

Cells normally die in a very controlled way, but these cancer cells balloon up to 2 or 3 times their size, giving the appearance of blistering.

And it’s this precise effect that gives EnAd potential to be a great cancer cell killer.

Cancer cells can disguise themselves from the body’s immune system, but when EnAd destroys cancer cells in the lab it leaves the ‘crime scene’ upturned, with lots of evidence carelessly left behind. Seymour’s team believe this could encourage the immune system to ring the alarm for other immune cells to come and investigate the scene.

And to test this further, they’ve been putting lots of versions of the virus to work in the lab.

Seymour’s team has made sure they’ve got the deadliest of cancer cell killers by using a tough training programme.

“Viruses are naturally good at killing cancer cells so even harmless ones have some ability to attack them,” says Dyer.

“But to find the best virus, we grow them repeatedly in cancer cells and compare them all head to head.”

It’s important that the virus can tell the difference between healthy tissue and cancer cells. So the team also tests them on healthy cells to make sure the viruses can’t grow in them.

“So at the same time we also look for the ones that are least able to infect normal cells,” says Dyer.

This tough selection process leaves the viruses with only one mission: to infect and destroy cancer cells.

EnAd has passed these lab examinations and is now being tested in an early stage clinical trial in a very small number of people.

“These trials are making sure the virus is safe and to find the best way to give it to the patient. Ideally we’d like to use an injection so the virus can get into the bloodstream and reach cells that have gone to other parts of the body,” says Dyer.

Some cancers can also become resistant to the ways in which treatments destroy them. But because EnAd has a different method of destroying cancer cells, Seymour’s team believes the virus might also be able to kill cancers that have become resistant to treatment.

Ultimately, the team hopes to test how it performs with other drugs and in specific types of cancer, bringing it that little bit closer to becoming a new ally for targeting cancer.

 

 

 

This blog post was originally published by Cancer Research UK. Author Gabi Beer.