UK breakthrough in lung cancer helps target patients at risk of relapse | Lung cancer

Seven years ago, Kelly Harrop worked at a stable while also regularly running in half marathons and 10k races. Then she started to suffer from digestive problems. Scans eventually revealed marks on her lungs. The subsequent diagnosis was straightforward. “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 tumor, followed by chemotherapy. But doctors knew there was a risk of the tumor returning, 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 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 tumors, which have the greatest diversity of mutations, have the worst clinical outcomes.

“After surgery and chemotherapy, about 70% of patients with lung cancer are cured. However, the remainder will relapse due to metastatic spread and we found that these cases tend to be linked to tumors with most chromosomal abnormalities,” said project leader Prof. Charles Swanton of the Francis Crick Institute in London.

Only 10% 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 recurrence by assessing the levels of their chromosomal abnormalities?

Recurrent tumors could be detected long before symptoms appear, buying patients crucial time. “In the early stages of lung cancer returning, the burden of disease is much less and the actions taken will have a much greater impact,” Swanton said.

The TRACERx team has succeeded in developing a technique that can separate patients who are certain to relapse from those who are much less likely to. One of the first patients to be involved in testing the new technique was Kelly Harrop.

“My blood was tested every three months, then reduced to every six months until, five years after my surgery and chemotherapy, the tests stopped and I was cleared,” she said.

The new technique, which is still completing its clinical trials, provides early warnings of a cancer returning while freeing recovering cancer patients who are not at risk of a tumor returning, like Kelly, from undergoing treatments. unnecessary extras. “That means we can reach the patients who need it most when they are most receptive to treatment,” Swanton said.

But Kelly’s case raises an important question. She had never smoked but still developed lung cancer. The disease is closely linked to smoking, but “never smokers” represent 10-20% of cases. Since then, research funded by TRACERx has uncovered an important risk.

“We found that air pollution is an important trigger for lung cancer. It generates an inflammatory response in the lungs, triggering an influx of white blood cells which, in turn, release signaling molecules that prompt the lung membrane to initiate a wound-healing response. Crucially, this response backfires if the cells harbor a specific mutation. The result is a tumor,” Swanton said.

“We found 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 the cells need the mutation and need to be exposed to air pollution to trigger an inflammatory response for the onset of cancer.”

The discovery is another important development in the battle against the disease and will be followed up next year when Cancer Research UK will commit a further £13m to the 10-year second 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 disease.

“Lung cancer is a form of genetic chaos unprecedented among other tumor types,” Swanton added.

“So if we can beat it, we can beat any cancer.”

UK breakthrough in lung cancer helps target patients at risk of relapse | Lung cancer

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