Breakthrough Study Reveals Origins of Lung Cancer Linked to Smoking

Key Findings

A recent study has unveiled the origins of lung squamous cell carcinoma (LUSC), the second most prevalent type of lung cancer, particularly affecting smokers. Conducted by researchers at University College London (UCL), in collaboration with the Wellcome Sanger Institute and the University of Cambridge, the study highlights the competitive dynamics of basal cells in the trachea.

Published in the journal Science, the research indicates that specific basal cells, which express the gene KRT5, outcompete other cell types and proliferate, eventually dominating the lung environment. This finding may pave the way for earlier detection and potential prevention strategies for lung cancer.

Lung cancer remains the leading cause of cancer-related mortality globally, often diagnosed at advanced stages where treatment options are limited. LUSC arises from cumulative cellular damage due to exposure to carcinogens, predominantly from tobacco smoke. The study aims to elucidate the transitions from healthy to precancerous states in lung cells.

Professor Sam Janes from UCL's Division of Medicine expressed the importance of understanding the cellular origins of LUSC. The research provides insight into how a subset of KRT5-expressing cells can proliferate and displace normal cells, leading to tumor formation.

To investigate the cells' origins, the research team utilized genetically modified mice to track KRT5-expressing basal cells over time. One cohort of the mice was exposed to carcinogens to monitor the impact on cellular behavior. Results indicated that in the carcinogen-exposed group, these basal cells expanded and infiltrated the lungs, while the control group maintained their original position in the trachea.

Dr. Sandra Gómez-López, the first author of the study, elaborated on the natural balance between basal stem cells and luminal cells within the airways. Carcinogenic exposure disrupts this balance, allowing populations of damaged basal cells to dominate and invade larger lung areas.

The research included single-cell RNA sequencing of tracheal cells from both mice and humans, establishing parallels between the two groups. The findings revealed that as damaged basal cells proliferate, other cell types, including luminal cells, diminish in number.

Furthermore, DNA sequencing of human lung samples from smokers indicated that precancerous lesions often originated from the same altered basal cell. This genetic insight may lead to the development of early detection tests and interventions targeting the initial stages of lung cancer, facilitating timely treatment.

Dr. Talisia Quallo from Cancer Research UK emphasized the importance of early detection, given that lung cancer is a leading cause of cancer-related deaths in the UK. The study's revelations about the cellular transitions leading to LUSC could inform future detection methods and preventative strategies.

Professor Peter Campbell from the University of Cambridge noted that identifying the specific environments in the lung that facilitate cancer development could help in predicting and detecting tumors at earlier stages, potentially improving patient outcomes.

Overall, this groundbreaking research underscores the importance of understanding cellular dynamics in lung cancer progression, offering hope for advancements in early detection and treatment.