It should have been a dream holiday, a perfect escape from England’s January chills for a retired couple. Terrence, 75, was relaxing on deck with a book, as the cruise ship slid through sapphire waters between Bali and Singapore.
The next thing he knew, his lung had collapsed.
His wife Maureen recalls: “He went, ‘I can’t breathe!’ and I thought he was joking. But of course he wasn’t.”
After a visit to the ship’s doctor – and two very uncomfortable days sailing – the couple reached Singapore where Terrence had surgery to repair the damage. Two weeks later, the couple flew back to the UK, their holiday cut frustratingly short.
“The surgeon in Singapore had been educated in London and knew about the NHS. He said, as soon as you get back to the UK, fix up with your GP to get either a scan or X-rays, and just keep an eye on it,” remembers Terrence.
But as Maureen recalls, there was a small cloud on the horizon. “The surgeon did tell us there was a little… little something at the bottom of the lung – a tiny little dot – but he wasn’t going to investigate it because he knew we had to fly home. He said just, you know, ‘keep an eye on that.’”
Another concern was the fact that Terrence had smoked for most of his life, starting when he was just 13, and had only quit six years earlier. So over the following months, Terrence had regular X-rays at the Princess Alexandra hospital near the couple’s home in Essex.
But by September 2013, that ‘small cloud’ had developed into something more threatening.
“The doctors spotted an anomaly,” he says. “The dot had changed its shape. And they weren’t happy, so they arranged a PET scan, and a biopsy. I’m not that naive to think that if something in your lungs changes shape… well, it isn’t good news.”
A few weeks later the results of the biopsy came back. It was cancer, and Terrence had surgery to remove a small tumour in his left lung.
Tracking lung cancer through time
About two years ago, about shortly before Terrence’s diagnosis, we announced plans for a pioneering study to transform the understanding of lung cancer – the world’s biggest cancer killer.
TRACERx is our largest single investment in lung cancer research. The UK-wide study set out to recruit and monitor 850 patients with early-stage non-small cell lung cancer, taking regular blood samples and scans, over five years.
It’s a vital project. Terrence was luckily diagnosed early, but lung cancer is often diagnosed late, when it’s already spread. So relatively little is known about how it develops, compared with other common forms of cancer. TRACERx aims to throw pretty much every modern monitoring technique at its participants in an effort to understand their disease and – ultimately – use this knowledge to help others.
And Terrence is taking part.
“The day before my operation, I was asked if I wanted to take part in a study. They explained that they’d track me – either with a scan or a blood sample – every three months, for the next five years,” he says. “It’s brilliant. Being regularly monitored by one of the biggest cancer research organisations in the world… it’s like winning the lottery!”
Terrence’s operation went well – all signs of cancer were removed and there didn’t seem to be any in his lymph nodes. He’s now cancer-free, and still being monitored by the TRACERx team.
“I’m trying to enjoy life even more now, because I think, we’ve had a near miss haven’t we?” he says.
Evolving tumours, evolving studies
TRACERx is now in its second full year. So how have things progressed?
“It’s been hard work,” says Cancer Research UK’s Professor Charles Swanton, the driving force behind the project – which involves six hospitals across the UK, and almost as many research centres. “With so many aspects to the study it’s been tough co-ordinating things across so many centres, and been a lot harder than I thought. But it’s going really well.”
The study has now recruited nearly 200 patients – just under a quarter of the overall target. And alongside all the original plans for DNA analysis (which we wrote about when the trial launched) Swanton’s team have opened up several new fronts.
“We’re now collaborating with a lab in the US at the Dana-Farber Cancer Center,” says Swanton, who recently moved with his team to the new Francis Crick Institute in London.
“An imaging team there lead by Hugo Aerts is looking at whether scans from TRACERx participants show anything that relates to the degree of genetic chaos we’re measuring in their tumour samples.” The aim, he says, is to develop a much easier, less invasive way to understand a patient’s disease than relatively costly DNA analysis.
“And we’ve also linked up with a lab at The Institute of Cancer Research in London, led by Yinyin Yuan,” he says. They’ll be looking at tumour samples from TRACERx to see if the interaction between a tumour and its surrounding neighbourhood – known as the ‘tumour microenvironment’ – also holds clues that could be exploited.
In another significant development, Swanton’s team is working with two pharmaceutical companies to set up clinical trials for TRACERx patients whose cancers come back after treatment – something that’s only possible because of the detailed molecular analyses being carried out as an integral part of the study.
The first, DARWIN1, will test whether patients whose cancers are caused by faults in a gene called EGFR will benefit from a drug called afatanib, which is designed to target these cancers.
The second trial, DARWIN II, will offer people a range of drugs targeted to faults in other genes, such as BRAF or Her2, to see if they can help. And patients whose tumours don’t carry any of these faults, will be offered treatment with one of a new class of immunotherapy drug called ‘checkpoint inhibitors’.
And it’s this area – immunotherapy – that Swanton thinks holds immense promise.
“In the last couple of years, we’ve really seen how drugs that target the immune system can produce dramatic responses in some patients and they’re becoming standard treatments in lung cancer. So the work we’re doing with Sergio Quezada’s lab at UCL is something I’m really excited about,” says Swanton.
“If we can work out how to harness the knowledge we’re generating in TRACERx to find immunotherapies that benefit more patients, then I think we’re really going to be onto something big.”
It’s almost like you’re giving a donation, but instead of giving money, you’re donating a bit of blood.
And it’s making researchers in other fields take notice too. TRACERx’s pioneering design has inspired scientists studying other hard-to-treat, poorly understood cancers – notably oesophageal and pancreatic cancers – to begin thinking along similar lines.
Taking part in such a hugely ambitious project is something that gives Terrence and Maureen huge comfort.
“It’s almost like you’re giving a donation, but instead of giving money, you’re donating a bit of blood, or whatever information you can pass on,” says Terrence. “And I think that’s brilliant. You’re donating your body, in a way, to research.”
Terrence and Maureen are shortly off on holiday again. “We’ve been married a long time, and we do everything for each other. We just want to do more stuff, don’t we?” says Terrence. “We just want to… wake up and smell the roses!”
And there’s a curious coincidence in this story. Many decades ago, Terrence used to work repairing ventilation systems in buildings in London. One of these buildings is now Cancer Research UK’s head office. You could say, in a roundabout and slightly different way, we’re now returning the favour.