The first signs of lung cancer spread can be found in blood samples and biopsies

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The new findings, published in Nature Medicine, provide data on which patients could be treated safely with milder therapies, such as surgery alone, and which may need additional treatments, including chemotherapy. The findings could also help researchers develop treatments for the most aggressive forms of lung cancer.

Around 47,000 people are diagnosed with lung cancer in the United Kingdom every year and less than one in five survive for five years or more. Researchers believe that a key reason why so few people survive lung cancer is that tumor cells evolve rapidly, developing resistance to current treatments and evading the body's immune system.

The TRACERx study of Cancer Research UK, which involves more than 750 patients from 13 UK hospitals, is examining how lung cancer cells evolve and spread through the blood, as well as how the immune system responds.

In the first of the new studies, Professor Caroline Dive, from Cancer Research Institute from the United Kingdom and his team, wanted to find out if it would be possible to predict which lung cancer would return after treatment. Just before surgery to remove lung tumors, the team took samples of the patients' blood. They searched the blood samples for cancer cells that had escaped the tumor and looked at the number and types of these cells.

“We supervised the patients for up to four years and found that those with the highest amount of tumor cells in their blood samples taken from the tumor site were also the ones most likely to suffer a recurrence,” explains the doctor.

“By observing an individual patient who unfortunately his cancer reappeared and spread ten months after surgery, we were able to identify the possible cause, he continues. We trace the origin of the tumor secondary to particular cells that escaped to the blood from the primary tumor at the time of surgery. ”

The second study was conducted by Dhruva Biswas, researcher of the Francis Crick Institute and Charles Swanton of University of London Cancer Institute (UCL).

They studied samples of lung tumors and found signs of what types of cancer were most likely to return after treatment, regardless of clinical measures such as size or stage.
Doctors already use individual biopsies taken of tumors at the point of diagnosis to help select the best treatment plan for each patient. However, previous research has shown that lung tumors are genetically unstable and evolve over time.

This evolution means that populations of cancer cells within an individual tumor may differ in different parts and from one biopsy to another, which limits the physician's ability to provide patients with an accurate prognosis.

“To overcome this problem, we have developed a new technique called ORACLE, explains Biswas, uses our knowledge of tumor evolution to look for stable genetic characteristics that we can find throughout the tumor. This is combined with a machine learning algorithm to identify characteristics that predict how aggressive a tumor is likely to be. ”

“These characteristics could be detected no matter what part of the tumor is sampled for the test, which means they could be a more accurate guide for predicting the future clinical outcome for patients,” he adds.

Professor Benny Chain, from UCL, and his team conducted the third study, focusing on the immune system of patients with lung cancer. Once again observing tumor biopsies, the team discovered that T cells were grouped between cancer cells.

This suggests that the patients' immune system was recognizing and trying to fight cancer. They also analyzed these cells to see what was unique about those who could recognize cancer.

“Each lung tumor is made up of a mixture of different cancer cells, which we suspect is helping lung cancer to confuse our immune system and, therefore, grow faster, says Professor Chain. However, our research shows that T cells can still detect cancer cells.

“We now believe that looking at a patient's T cells in action against lung cancer could give us clues about how a treatment is working for that individual patient. Our research also suggests the possibility that specific groups of patients' T cells can be isolated and adapted to help treat their tumor more effectively, ”he says.

Professor Charles Swanton, Clinical Chief of Cancer Research UK, which leads the TRACERx project, adds that “research has shown that lung cancer is an extremely complicated disease with a mosaic of different cells that make up each individual tumor. We believe that understanding this variation, how these different cells are produced and how immunity detects this system variation will be key to improving lung cancer survival, ”he says.

“Thanks to these findings, we know much more about how lung cancer changes, spreads and evades treatment. As our collaboration continues, we will develop these discoveries and, ultimately, we will develop tests to guide and improve the way lung cancer is treated in the future, ”he advances.


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