Disrupting tumour defences in pancreatic cancer
A short stroll across the peaceful gardens of Charterhouse Square in East London, and through what appears to be a Tudor gatehouse, lies Barts and The London School of Medicine and Dentistry. History adorns the plaques and signs stuck to the side of buildings - a wonderful mix of old and new.
William Harvey has a building named after him here. The 16th and 17th Century physician was ‘Physician Extraordinary’ to King James I - the first uniting King of Scotland and England and son of Mary Queen of Scots. He was also one of the first people to describe in detail how the circulatory system worked through pumping blood to the brain and body via the heart. Next to the building that bears his name, where scientists continue to study cardiovascular biology, is the Barts Cancer Institute (BCI).
It’s here that researchers are also dissecting the inner workings of a biological system. Only this one is cancer, which instead of pumping life through the body, grows relentlessly and chaotically, devouring and devastating everything it touches. One of the team leaders here is Dr Angus Cameron, whose team are working on improving treatment for a cancer with one of the worst outcomes.
An unusual accident
“Thanks for not noticing the limp” said Angus as he chaperoned me to his office. I was there to talk to him about the work he was doing with funding from Worldwide Cancer Research and the progress his team were making. His limp was completely unnoticeable, but I learn it’s been a yearlong recovery.
“I’ve been on crutches for the past year, recovering from a rather unusual accident. I was running the London Marathon last year raising money for brain tumour research after my good friend Nick passed away, and I was in the home straight, literally 50m from the line and my femur snapped!”
Not deterred by what must have been a painful experience, Angus is determined to get back and complete the marathon for Nick as soon as possible. Angus’s sense of determination reflects in his excitement and drive to better the lives of cancer patients through his research.
“Our lab is focused on the interaction between normal cells and cancer cells. And we are specifically interested in pancreatic cancer. The biology of pancreatic cancer is quite unusual because tumours are largely made up of fibrotic tissue, which is full of a normal cell type called fibroblasts. In fact, cancer cells often only make up 10-20% of the mass of a pancreatic tumour.”
Cancers unseen shield
In tumours of the pancreas, these fibroblasts are hijacked by the cancer cells and help them to spread into the nearby tissue. They also act as a protective shield, preventing drugs from being able to penetrate into the tumour, and preventing cells of the immune system from accessing the tumour where they can help to eradicate cancer cells.
“Our project is trying to specifically target the activation of fibroblasts by cancer cells in order to help make treatments such as immunotherapy and chemotherapy work better for pancreatic cancer patients,” explained Angus.
Pancreatic cancer is often diagnosed at an advanced stage when it is too late for treatments to have any real positive effect. Patients often only survive for a year or so after their diagnosis, and in many cases, the patient may only live a couple of months or even weeks. This grim picture hasn’t changed in 40 years.
Three steps forward
Angus’s project started in April 2018 and was only possible thanks to a partnership set up between Worldwide Cancer Research and Pancreatic Cancer Research Fund. His work focusses on a particular network of proteins found in fibroblasts that helps them to stay in communication with pancreatic cancer cells. Reflecting on the achievements of the past year, Angus told me that there are three ways in which they’ve really made progress.
“The first thing we’ve discovered is how this network inside fibroblasts sends signals into the nucleus to drive changes in gene expression that allows them to communicate with cancer cells and change the way the tumour behaves.”
“We’ve also fully established our in vivo model, and this is a tumour model in mice, which we are using to test how targeting this network or proteins will affect the growth of real tumours. This is a critical step for taking our findings towards the clinic.”
“And finally, we’re very excited because we’ve got our drug discovery pipeline up and running. In the next few weeks, we will start screening tens of thousands of chemical compounds to look for new drugs that specially disrupt the network in fibroblasts. And these will be the precursors for drugs that we will one day be able to test further and hopefully take into clinical trials.”
Live like Nick
As I walked back across sunny Charterhouse Square in the shadow of such inspiring science, it seemed all too easy to get lost in the detail of what I had heard in Angus’s office, and forget why places such as BCI and the William Harvey Institute exist. Then I recalled a story Angus told me about his friend Nick and was reminded of all the people that research strives to stop us losing in the future:
“My friend Nick was vivacious, loud, funny, great company. He also loved to dress well and amassed a crazy collection of scarves over the years. It was almost a trade mark. After his death his brother and closest friends inherited his scarf collection and we now all have a couple as reminders of our friendship. When I wear it, it reminds me to stay positive, keep perspective and live life to the full. Just as Nick did.”