Seven years ago, Kelly Harrop was working at a stables while also running regularly in half marathons and 10k races. Then she began to suffer digestive problems. Scans eventually revealed marks on her lungs. The subsequent diagnosis was direct. “I had lung cancer. It was a shock. I was fit, healthy and had never smoked,” she told the Observer.
Kelly had surgery to remove the tumour, followed by chemotherapy. But doctors knew there was a risk of the tumour reappearing, so they enrolled her in a new research programme, TRACERx. Funded by Cancer Research UK, the £14m project was set up 10 years ago to investigate how lung tumours arise and evolve. A total of 850 patients with early-stage lung cancer were studied and followed from diagnosis to treatment.
An early breakthrough involved the discovery that genetically unstable tumours, which have the greatest diversity of mutations, have the worst clinical outcomes.
“After surgery and chemotherapy, around 70% of lung cancer patients are cured. However, the rest will relapse due to metastatic spread and we have found these cases tend to be linked to tumours with the most chromosomal abnormalities,” said project leader Prof Charles Swanton, of London’s Francis Crick Institute.
Only 10% of those who suffer such relapses will be alive after five years, added Swanton. So could a way be found to identify patients at high risk of recurrence by assessing levels of their chromosomal abnormalities?
Returning tumours could then be spotted long before symptoms appeared, buying patients crucial time. “In the very early stages of a lung cancer’s return, the disease burden is much lower and actions taken then will have a much greater impact,” said Swanton.
The TRACERx team succeeded, developing a technique that can segregate patients who will definitely relapse from those who are far less likely to. One of the first patients to be involved in trials of the new technique was Kelly Harrop.
“My blood was tested every three months, later reduced to every six months until, five years after my surgery and chemotherapy, the tests were stopped and I was given the all clear,” she said.
The new technique, which is still completing its clinical trials, provides early warnings of a cancer’s return while freeing recuperating cancer patients who are not at risk of a tumour’s return, such as Kelly from undergoing unnecessary additional treatments. “It means we can target patients that are most at need when they are most receptive to treatment,” said Swanton.
But Kelly’s case raises an important issue. She had never smoked but still developed lung cancer. The disease is closely linked to smoking, but “never smokers” account for 10-20% of cases. Research funded by TRACERx has since uncovered a key risk.
“We have found that air pollution is an important trigger of lung cancer. It generates an inflammatory response in the lungs, triggering an influx of white cells which, in turn, releases signalling molecules that induce the lung’s membrane to initiate a wound-healing response. Crucially, this response goes awry if cells harbour a particular mutation. The result is a tumour,” said Swanton.
“We find these rare mutations occur in a very small number of cells that increase in frequency as part of the natural ageing process,” he added. “We found cells need the mutation and have to be exposed to air pollution generating an inflammatory response for a cancer to start.”
The discovery is another key development in the battle against the disease and will be followed up next year when Cancer Research UK commits a further £13m to the second 10-year phase of its lung cancer research programme, TRACERx Evo, which will build on past discoveries and study the role of air pollution and other factors in the disease.
“Lung cancer is a form of genetic chaos that is unprecedented among other tumour types,” added Swanton.
“So if we can beat it, we can beat any cancer.”
