Can Northern Ireland win the race to cure cancer?
Words Lucy Jolin / Illustration Jimmy Turrell
Monday, 19 June 2023
Queen’s researchers are leading on some of the most exciting work in cancer research. Now the world is beginning to take notice.
Imagine a world where cancer is no longer a deadly threat, but just another disease you get treatment for and then get better.
It might sound like science fiction but, for many, a cure for cancer is already a reality – and Queen’s researchers and clinicians are on the front line of finding new ways to tackle the disease, in all its many forms. And the world is sitting up and taking notice.
“Right now, Belfast is a very exciting place to be,” says Dr Robert Ladner, Reader at the School of Medicine, Dentistry and Biomedical Sciences and CEO of the drug company CV6 Therapeutics. His company is about to launch the world’s first human clinical trials of CV6-168 – one of the first cancer drugs to be developed in Belfast.
New cancer drugs are rare; new cancer drugs that come out of an academic startup even more so. But the evolving cancer research ecosystem in Northern Ireland has made it possible. “This could be a blockbuster drug,” says Ladner. “If it is successful – and I can’t say that it will be until we do our clinical trial – this is something that could really alter what’s going on in cancer treatment. As a cancer scientist, this is a once-in-a-career opportunity."
Why is Ladner so excited? The new drug could be used to treat many different types of cancer. It works alongside an existing, well- established and common drug – 5-FU – which is already used to treat millions of cancer patients every year. While 5-FU works by stopping cancer cells making new DNA, meaning that they can’t grow, when combined with 5-FU, CV6-168 attacks them on another front – by tricking them into thinking that they have been infected with a virus.
“We’re invoking the body’s ancient mechanisms of identifying viral DNA in cells – causing the cancer cells to signal to the immune system and get it working,” explains Ladner. “Our hypothesis is that we are going to enable 5-FU – one of the most important drugs ever discovered – to work on a completely different level.”
REASONS FOR OPTIMISM
Ladner has made it his life’s work to find a new way to treat cancer, first at the University of Southern California before moving his entire team to Queen’s, and specifically to the Patrick G Johnston Centre for Cancer Research (PGJCCR), in 2015. The advantages of Belfast were significant, he says: generous grant support from Invest Northern Ireland, tax incentives encouraging research and development, a tremendously skilled workforce, affordable housing for his team and, of course, the cutting-edge facilities and expertise available at the PGJCCR.
What makes the research environment of the PGJCCR really stand out, says Professor Chris Scott, Dean of Research, is its close links with the Cancer Centre at Belfast City Hospital – almost a third of investigators at the PGJCCR are clinicians who also work at the hospital. “That’s important, because it means we’re answering the right questions. I’m a scientist. I’m not a clinician. I might come up with solutions to problems that, maybe, are not really that important. But if clinicians tell you where the current problems are, you’re more likely to develop solutions or insight that are going to have impact in the clinic.”
One area that is getting a lot of attention at the moment off the back of the Covid pandemic is the generation of vaccines against cancer – and a new company, AilseVax Ltd, spun out from the Centre and Trinity College Dublin, is aiming to find one such vaccine. “We’re very excited about where AilseVax will go, and how they can develop new vaccine technologies to train the immune system to eradicate tumour cells that could have less potential side-effects than current therapies,” says Scott.
And while work on a cancer vaccine is just beginning, there are also reasons for optimism in efforts to build on existing drugs as
a way of getting new treatments to patients fast. Much of Dr Katrina Lappin’s work, for instance, is focused on drug repurposing – discovering new applications for drugs that are already approved for clinical use.
“Using an approved drug for a new purpose means you don’t need to do phase 1 clinical trials – you can go straight to phase 2 to find out how well the drug works,” she says. “A brand-new drug can take up to 15 years and millions of pounds to get to clinic. If you’re using a drug that has already been through the first stage, you halve that time.”
Her current work examines a genetic mutation known as SF3B1, which can make it more likely that you’ll get certain cancers. But the mutation could also be a way into targeting these cancers more efficiently. Lappin’s work has shown that cancer cells where SF3B1 is mutated are more sensitive to drugs known as poly-ADP ribose polymerase (PARP) inhibitors. These drugs stop PARP – a protein – from repairing cancer cells, which messes up the way they normally repair.
“There are multiple ways to repair a cell,” she says. “So, if a cell has a mutation that makes one way of repair impossible, it will rely more heavily on the alternatives. The PARP inhibitor can target this other pathway, giving the cell no option but to die. It should also more specifically target the cancer, reducing associated side effects as well.” And that matters, because for Lappin, it’s personal. “When I was five, my granda passed away with acute myeloid leukaemia,” she says. “He was diagnosed and died two weeks later. I love knowing that the work I’m doing might improve outcomes for patients.”
SURPRISING INSIGHTS
Of course, cancer research isn’t just about drugs – data also plays a key role. Professor Mark Lawler is passionate about using data to make a difference. “It’s not just about doing the research. What happens next? How does research develop into a change in cancer policy that means real things to real people?” His work on the impact of Covid on cancer found that 100 million people in Europe had not had cancer screening tests for breast, cervical and bowel cancer. Up to a million people may have had a missed or undiagnosed cancer. Surgery and chemotherapy dropped by 50 per cent.
Lawler’s data enabled the European Cancer Organisation to develop a campaign called Time to Act, which he co-led, with a simple message going out to patients: don’t let Covid-19 stop you from tackling cancer. It has been incredibly successful – cited by the European Commissioner for Health and Food Safety, Stella Kyriakides, and Ursula von der Leyen, President of the European Commission. The work won the 2021 Royal College of Physicians Excellence in Patient Care Award and the prestigious 2022 European Communique Award, recognising its significant impact.
Now, Lawler and his team have turned their attention to another basic but vital question: are we doing cancer research in the most effective way possible? Their European Cancer Groundshot has been seminal, highlighting what needs to be done on the ground.
And his analysis of cancer research activity in Europe has turned up some unexpected insights. “For example, lung cancer is 21 per cent of the cancer burden,” he says. “But just four per cent of research efforts, resources and funding go on lung cancer. So, there’s a disconnect between the problem and what we’re currently doing to try and address it.”
But it’s not enough to just do the research. Lawler’s team have now produced a 12-step plan with supporting data showing that if their recommendations are followed, 70 per cent of cancer patients could live for 10 years or more by 2035. This ‘70:35’ vision is a hugely ambitious target, says Lawler, but when it comes to cancer, you have to think big.
And clinicians seeing patients on the front line are already beginning to see the real-world impact. Prostate cancer is the most commonly diagnosed male cancer in the UK: about one in eight men can expect to be diagnosed with it in their lifetime. And it’s complicated. “It’s not one disease, so there isn’t just one treatment,” says clinical oncologist Professor Joe O’Sullivan. “It’s a spectrum that ranges from very aggressive lethal prostate cancers to prostate cancers that don’t need treatment at all.”
INCREDIBLE ADVANCES
At the newly created Prostate Cancer Centre of Excellence, O’Sullivan and his team are running crucial studies of new drugs and treatment combinations aimed at men with the most aggressive forms of cancer, as well as developing new diagnostic tests to help with better patient-specific decision making. Last year, they completed phase 1 of a world-first trial, known as ADRRAD, among men presenting with advanced prostate cancer that has spread to the bone. It combined hormone therapy, chemotherapy, highly targeted radiotherapy and six injections of a radioactive drug called radium 223. “So far, we’ve seen excellent feasibility and tolerability, and very encouraging efficacy or hopefully potentially life-extending ability,” says O’Sullivan. “When I first started treating prostate cancer, men with these cancers may have lived for two years. Now, we are expecting them to live six, seven, eight years and beyond.” The prostate cancer clinical research programme is part of Queen’s wider clinical trials programme at the Northern Ireland Cancer Centre, which has recruited thousands of patients over the last 20 years.
Those past two decades have seen incredible advances in cancer research in Northern Ireland – and this may be the tipping point, the dawn of a new world. A world in which cancer research funds are targeted at the cancers that need them most; in which, if you do get cancer, it’s diagnosed early; in which there are a multitude of effective treatments with few side effects, giving you not just a longer life, but a much happier one. It’s a world that may soon be right here.
FURTHER INFORMATION
Read the full version of Lanyon Issue 2
To support health fundraising at Queen’s University, visit the Development and Alumni Relations Office website or contact Teresa Sloan, Head of Health Fundraising.
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