A new study has uncovered the cell where a common type of lung cancer begins, and how it spreads through the lungs. This discovery could help doctors detect or even prevent lung cancer at an earlier stage, when treatment has the best chance of success.
Researchers from University College London (UCL), the Wellcome Sanger Institute, and the University of Cambridge studied both mice and human samples to understand how lung squamous cell carcinoma (LUSC), the second most common type of lung cancer, starts and develops.
The results, published in Science, show that the cancer begins from a special group of cells found in the windpipe (trachea), called basal cells. These cells express a gene called Krt5, which helps form the structure of cells.
Lung cancer is the leading cause of cancer-related deaths globally, mostly because it is usually diagnosed too late. LUSC commonly develops due to long-term exposure to harmful substances like tobacco smoke.
Over time, this exposure damages cells in the airways, creating patches of abnormal tissue—called precancerous lesions—that can eventually turn into cancer. Until now, scientists didn’t know exactly which cells were responsible for this early stage.
In the study, researchers tracked the behavior of Krt5-expressing basal cells in mice. In one group, mice were exposed to cancer-causing substances similar to those in cigarette smoke. In the other group, mice were not exposed. In the exposed group, researchers saw that some of the basal cells began to multiply and move beyond their usual place in the trachea.
These cells expanded and started taking over larger parts of the lungs. Eventually, they became the starting point for tumors. In contrast, in mice that were not exposed to the carcinogens, these cells stayed in place and did not spread.
The study also revealed that as these damaged basal cells spread, they change the normal balance of cell types in the lungs. Under healthy conditions, basal cells divide to produce more basal cells or become luminal cells, which include secretory cells (which protect the lungs) and ciliated cells (which help move particles out of the airways).
But in lungs exposed to toxins, this balance breaks down. A different group of cells, known as transitional cells that express a gene called Krt13, became more common. Meanwhile, useful luminal cells became fewer.
To check if the findings apply to humans, the team also analyzed lung and windpipe tissue from smokers and non-smokers. They found that in smokers, cells in different parts of the lung—even in both lungs—could be traced back to the same damaged basal cell.
This means that a single damaged cell can spread and take over large areas of the lung, increasing the risk of developing cancer.
This research could help scientists create new ways to detect lung cancer much earlier than is currently possible. If doctors can identify the specific changes in these basal cells before they turn cancerous, they may be able to step in and stop the disease from developing.
There’s also hope that new drugs could be developed to stop these cells from becoming dominant in the lung in the first place.
Dr. Sandra Gómez-López, the study’s first author, explained that under normal conditions, different cell types in the lung live in balance. But when people are exposed to substances like tobacco smoke, that balance is lost. The damaged basal cells gain an advantage, multiply, and start to crowd out healthy cells—creating the first steps toward cancer.
Professor Sam Janes, one of the senior researchers, said the team’s goal is to one day prevent lung cancer before it starts, or at least catch it very early. Identifying the “cell of origin” and understanding how it spreads gives scientists a clearer path toward this goal.
Experts who were not involved in the study also see promise in the findings. Dr. Talisia Quallo from Cancer Research UK noted that early detection is key in fighting lung cancer, and this research could eventually lead to new screening tools or prevention strategies.
Professor Peter Campbell added that understanding why cancer appears in certain parts of the lung could allow doctors to watch for these risky areas in patients and plan early treatments.
In summary, this study shows that lung squamous cell carcinoma starts from a small group of damaged basal cells in the trachea. These cells multiply and invade the lung, disrupting normal tissue and increasing cancer risk. The findings bring hope for earlier detection and new treatments that could stop the disease before it takes hold.
If you care about lung health, please read studies about marijuana’s effects on lung health, and why some non-smokers get lung disease and some heavy smokers do not.
For more information about health, please see recent studies that olive oil may help you live longer, and vitamin D could help lower the risk of autoimmune diseases.
The research findings can be found in Science.
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