Kelly underwent surgery to remove the tumor, followed by chemotherapy. But doctors knew there was a risk of the tumor coming back, so they enrolled her in a new research program, TRACERx. Funded by Cancer Research UK, the £14 million project was set up 10 years ago to investigate how lung tumors form and develop. A total of 850 patients with early-stage lung cancer were studied and followed from diagnosis to treatment. An early discovery included the discovery that genetically unstable tumors, which have the greatest variety of mutations, have the worst clinical outcomes. “After surgery and chemotherapy, about 70% of lung cancer patients are cured. However, the rest will relapse due to metastatic spread and we have found that these cases tend to be associated with tumors with the most chromosomal abnormalities,” said project leader Professor Charles Swanton, of the Francis Crick Institute in London. Only 10 percent of those who suffer such relapses will be alive after five years, Swanton added. So could a way be found to identify patients at high risk of relapse by assessing their levels of chromosomal abnormalities? Recurring tumors could then be detected long before symptoms appear, buying patients critical time. “In the very early stages of a lung cancer returning, the burden of the disease is much lower, and actions taken then will have a much greater impact,” Swanton said. The TRACERx team has succeeded, developing a technique that can separate patients who are certain to relapse from those who are much less likely. One of the first patients to take part in trials of the new technique was Kelly Harrop. “My blood was checked every three months, later it was reduced to every six months until, five years after my surgery and chemotherapy, the tests stopped and gave me the all clear,” he said. The new technique, which is still completing clinical trials, provides early warnings of a cancer’s return while freeing recovering cancer patients who are not at risk of tumor recurrence, like Kelly, from unnecessary additional treatments. “It means we can target patients who are most in need when they are most receptive to treatment,” Swanton said. But Kelly’s case raises an important issue. He had never smoked, but still developed lung cancer. The disease is closely associated with smoking, but “never smokers” account for 10-20% of cases. TRACERx-funded research has since revealed a key risk. “We found that air pollution is an important factor in causing lung cancer. It creates an inflammatory response in the lungs, triggering an influx of white blood cells, which, in turn, release signaling molecules that cause the lung membrane to initiate a wound-healing response. Crucially, this response goes awry if the cells harbor a particular mutation. The result is a tumor,” Swanton said. “We find that these rare mutations occur in a very small number of cells that increase in frequency as part of the natural aging process,” he added. “We found that cells need the mutation and need to be exposed to the air pollution that creates an inflammatory response for a cancer to start.” The discovery is another key development in the fight against the disease and will be followed 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 of the role of air pollution and other factors in disease. “Lung cancer is a form of genetic chaos that is unprecedented among other types of tumors,” added Swanton. “So if we can beat that, we can beat any cancer.”
