Origins of common lung cancer that affects smokers discovered
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Image of a lung lobe from a carcinogen-exposed mouse. Cells expressing the basal cell marker KRT5 have been fluorescently labelled and can be seen spreading throughout the bronchial tree
view moreCredit: UCL
The ‘cell of origin’ of the second most common lung cancer and the way that it becomes dominant in the lung have been discovered, in a new study in mice and humans from researchers at UCL, the Wellcome Sanger Institute and the University of Cambridge.
The study, published in Science, found that a population of basal cells1 found in the trachea (windpipe) outcompetes other cell types and becomes dominant, eventually invading and occupying large areas of the lung.
It is from these cells, which express a gene called Krt5 that helps to build the structure of cells, that lung squamous cell carcinoma (LUSC) eventually develops. The research team say the findings raise the prospect of earlier detection, and perhaps even prevention, of lung cancer in future.
Lung cancer remains the leading cause of cancer-related deaths worldwide, frequently presenting at a late, incurable stage. LUSC is the second most common subtype of lung cancer and develops when cells accumulate continuous damage from exposure to toxins, usually from smoking.
As a result, the cells become increasingly disorganised and eventually form areas of damaged tissue (precancerous lesions) in the lining of the airways. But the biological changes that occur in the cells during the transition from a normal to a precancer state are unknown.
Professor Sam Janes, senior author of the study from UCL Division of Medicine, said: “In this study, we set out to understand the changes that occur prior to the development of lung squamous cell carcinoma and which cell type this cancer arises from.
“We found that a subset of cells expressing the gene Krt5 becomes dominant and starts pushing out normal cells. This expansion becomes dramatic and eventually the descendants of just a few cells that originated in the trachea invade and conquer normal cells, in some cases going on to populate whole lobes of the lung. It is these cells that eventually form tumours.
“By understanding the ‘cell of origin’ where these changes begin and how they develop, the ambition is that we will be able to design strategies to prevent lung cancer occurring in the first place or at least detect it much earlier.”
To investigate the origins of LUSC, the team labelled Krt5-expressing basal cells in the trachea of two groups of mice so that the descendants of these cells could be tracked over time.
One group of mice was then exposed to a carcinogen (cancer-causing substance), to observe how this affected the normal behaviour of the cells in the airways.
In this group, some of these basal cells gradually multiplied before spreading into the lungs, whereas in the control group the basal cells and their descendants remained in their original location in the trachea.
Dr Sandra Gómez-López, first author of the study from UCL Division of Medicine, said: “Under normal circumstances the lining of the airways is made up of basal stem cells, as well as luminal cells helping to protect the lung. When basal cells divide, they give rise to new basal cells or to luminal cells. Luminal cells perform key functions in the airways, with secretory cells producing protective substances, or ciliated cells that help move inhaled particles.
“There is a natural balance between the different cell populations and types, but when these cell populations are exposed to carcinogens like those found in tobacco smoke, this balance is disrupted. Our experiments have shown that populations of cells originating from just a few damaged basal cells in the trachea gradually become dominant, taking over large areas of the lung.”
Additional single-cell RNA sequencing of tracheal cells from mice (comparing healthy control cells vs those exposed to a carcinogen) and humans (comparing cells from non- vs current smokers) revealed that as these damaged basal cells colonise the airways, a population of transitional cells expressing a different gene, Krt13, also becomes more abundant, while some luminal cell types become scarce.
The researchers also performed DNA sequencing of human trachea and lung samples from people who had smoked. As in the mouse experiment, the results showed that cells from separate precancerous lesions, sometimes in both lungs of the same person, were again descended from the same damaged basal cell.
The researchers aim to use this knowledge to develop tests to detect the earliest steps towards lung cancer that occur when cells appear normal, in the hope of facilitating earlier interventions. Understanding how these cells become so dominant in the lung may also enable the development of new drugs to stop this occurring, raising the prospect of preventing these cancers in the future.
Dr Talisia Quallo, Research Programme Manager in Early Detection and Diagnosis at Cancer Research UK, said: “Lung cancer is the most common cause of cancer death in the UK, accounting for one in five of all cancer deaths. The disease is often caught late, so it's important that we find ways to detect lung cancer earlier, when there is the best chance of treating it successfully.
"This research reveals the early cellular steps preceding the development of lung squamous cell carcinoma, a common form of lung cancer, and identifies the cell type from which this cancer develops. More research is needed, but in future this information could help scientists to develop new ways to detect the disease earlier or even prevent it from occurring.”
Professor Peter Campbell, an author of the study from the University of Cambridge and previously at the Wellcome Sanger Institute, said: “Understanding why lung cancer develops where it does can help researchers and clinicians find new ways to predict or detect tumours early, helping to give the best possible outcomes.
“For me, one of the most interesting aspects of our research was discovering that squamous cell lung cancer develops from a precursor cell once it has found a particular environment in the lung, with space to grow and genetically change. We found that when these specific environments arise, they dramatically increase the risk of lung cancer. In the future, it could be possible to look for these sections in those at risk of cancer and develop treatment plans to prevent or treat lung cancer as early as possible.”
Notes to Editors:
For more information, please contact:
Dr Matt Midgley
+44 (0)20 7679 9064
1 Basal cells are a type of stem cell found in epithelial tissue, such as the skin and lining of the airways. Basal cells allow these tissues to constantly regenerate by replenishing the various cell types required by that part of the body throughout life.
Publication:
Sandra Gómez-López et al. ‘Aberrant basal cell clonal dynamics shape early lung carcinogenesis’ is published in Science and is strictly embargoed until Thursday 1 May 2025 at 19:00 BST / 14:00 ET.
DOI: https://doi.org/10.1126/science.ads9145
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Journal
Science
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Aberrant basal cell clonal dynamics shape early lung carcinogenesis
Article Publication Date
1-May-2025
By 2030, 40% increase in tobacco-related coronary heart disease deaths anticipated
Separate studies uncover the continued risk of tobacco and cannabis use for heart disease deaths and complications
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SCAI Scientific Sessions 2025
view moreCredit: Society for Cardiovascular Angiography & Interventions
Washington, D.C. – May 1, 2025 – New clinical results from multiple studies show coronary heart disease death associated with tobacco use is anticipated to rise up to 40% in the next five years and people with cannabis use disorder are 50% more likely to experience cardiogenic shock, acute myocardial infarction, and arrhythmias. These studies were presented today at the Society for Cardiovascular Angiography & Interventions (SCAI) 2025 Scientific Sessions.
Tobacco and cannabis are two of the most used substances in the United States, with 22% of Americans aged 12 or older reporting any past-month tobacco use and 13.0 % reporting any past-month cannabis use. As the rise in use continues, more research is needed to understand the impact and better inform patient care.
“Despite major public health campaigns to raise awareness for the harms of tobacco and cannabis, usage is still commonplace as we continue to see their effects on cardiovascular health,” said SCAI President James B. Hermiller, MD, MSCAI. “This new research presented at SCAI’s 2025 Scientific Sessions is vital for quantifying the burden tobacco and cannabis use have on certain communities, prompting tailored action and additional education for the patients that need it the most.”
Tobacco Use-Related Deaths on the Rise at a Significant Rate: Black Women and American Indian Most at Risk
Ischemic heart disease, also known as coronary heart disease, is a condition where the heart weakens due to reduced blood flow from narrowed or blocked coronary arteries. Studies have linked tobacco use to ischemic heart disease-related mortality and morbidity. Subsequently, government and public health organizations have launched campaigns to raise awareness and reduce deaths associated with tobacco use.
Researchers analyzed national CDC-WONDER data from 1999-2020 on ischemic heart disease mortality related to tobacco use (IHD-T) in individuals aged 25 and older. Death rate per 100,000 and annual and average annual percentage changes (APC, AAPC) were analyzed to identify trends and calculate projections until 2030.
In 1999, 4,669 deaths occurred in relation to IHD-T, increasing 14-fold to 56,367 deaths by 2020. Data projected a 43.7% increase in IHD-T-related deaths by 2030 (80,985). While the mortality trends in females decreased in 2005 (APC 2.68) and 2015 (APC 0.53), males saw the opposite with a sharp uptick in deaths until 2005 (APC 40.39). American Indian/Alaska Native, Black Americans, and Asian/Pacific Islander groups saw a sharp early rise in death rates, with annual changes over 30%, before those rates eventually leveled off. Overall, death rates continued to rise steadily across all racial groups, with average annual increases of over 10%. However, in women, Black women saw an average annual rise of 10.39%, and white men saw the highest average annual rise of 12.01%.
“Tobacco-related ischemic heart disease is not just a problem of the past. It is still a major cause of death today. Our analysis found that risks are not evenly distributed, as Black women experienced the higher annual increases in mortality compared to white women. If we hope to design more targeted interventions, it’s vital for clinicians to recognize that certain racial and geographic groups are disproportionately affected,” said Roopeessh Vempati, MD, PGY 1 Internal Medicine at Trinity Health Oakland in Pontiac, Mich. and Wayne State University in Detroit, Mich and lead author of the study. “Stronger, more targeted action through preventative cardiology and public health strategies are needed to reverse these trends and protect the most vulnerable.”
This abstract is published in the SCAI Abstract Supplement, which appears in SCAI’s official journal, JSCAI. You can access it here: https://doi.org/10.1016/j.jscai.2025.103178.
Data Reveals Heart Failure Patients with Cannabis Use Disorder 50% More likely to Experience Heart Attack
Cannabis use disorder (CUD) is a condition where individuals have a problematic pattern of cannabis use, leading to distress or impairment in day-to-day life and impacts. As the condition becomes more prevalent, this analysis aims to understand the association of heart failure (HF) hospital admissions and CUD.
Through National Inpatient Sample (NIS) data from 2016 to 2020, researchers identified patients who were admitted with HF and divided the population into two groups based on secondary diagnosis of CUD. Mortality risk and in-hospital complications in the HF/CUD group were analyzed and compared to the HF/non-CUD group.
The analysis revealed patients with HF and CUD experienced a greater risk of serious cardiovascular events. Retrospective data found 1,372,419 patients were admitted with HF during the study duration, with 19,445 (1.4%) of patients having CUD. While the HF/CUD group displayed higher odds of cardiogenic shock (27% more likely), acute myocardial infarction (50% more likely), and arrhythmias (48% more likely) as compared to the HF/non-CUD group, they also revealed lower odds of mortality (50% less likely), and respiratory failure (75% less likely).
“We were surprised to discover individuals with cannabis use disorder and heart failure are at a lower risk of mortality than those without the disorder,” said Syed Ishaq, MD, Internal Medicine resident at the Sinai Hospital of Baltimore in Md., and lead author of the study. “However, despite a lower chance of death, they are at significantly greater odds of developing other related cardiovascular conditions like heart attack or irregular heartbeat. This understanding is necessary for doctors and public health professionals to warn individuals of the potential side effects of consistent cannabis use from the start, even before heart failure occurs.”
Additional research into HF patients with accompanying substance use disorder is warranted.
This abstract is published in the SCAI Abstract Supplement, which appears in SCAI’s official journal, JSCAI. You can access it here: https://doi.org/10.1016/j.jscai.2025.102905.
Session Details:
Friday, May 2, 2025;1:25-1:55 PM ET
Walter E. Washington Convention Center, Exhibit Hall D
Thursday, May 1, 2025;3:30-4:15 PM ET
Walter E. Washington Convention Center, Exhibit Hall D
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About Society for Cardiovascular Angiography & Interventions (SCAI)
The Society for Cardiovascular Angiography & Interventions, established in 1978, stands as the primary nonprofit medical society dedicated to representing invasive and interventional cardiology. SCAI's mission is to guide the global interventional cardiovascular community by fostering education, advocacy, research, and upholding standards for quality patient care. For more than 40 years, SCAI has exemplified professional excellence and innovation worldwide, cultivating a reputable community of over 5,000 members committed to advancing medical science and providing life-saving care for individuals, both adults and children, affected by cardiovascular disease. For more information, visit https://scai.org/.
For more information about the SCAI 2025 Scientific Sessions, visit https://scai.org/scai-2025-scientific-sessions. Follow @SCAI on X for the latest heart health news and use #SCAI2025 to follow the latest discussions.
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