Duke study reveals new origin of deadly lung cancer, paving way for innovative treatments

A new study by Duke researchers marked a major shift in understanding one of the deadliest forms of lung cancer.

On Wednesday, researchers released a new study that found small cell lung cancer (SCLC) likely begins in basal stem-like cells rather than in specialized lung cells called neuroendocrine cells.

The study suggests basal cells can “give rise to tumors in both the classic neuroendocrine form and a tuft-like form.”

“This discovery reshapes our understanding of how small cell lung cancer begins,” said the study’s senior author, Trudy G. Oliver, Ph.D., professor in the Department of Pharmacology and Cancer Biology at Duke University School of Medicine.

The “tuft-like form” is connected to poor patient outcomes and resistance to current treatment. Researchers said this new discovery allows them to explore new strategies to prevent the disease before it takes over the immune system and spreads.

“Our models, for the first time, reflect the full complexity of the disease, allowing us to study and target its most dangerous forms,” Oliver said.

Researchers said that by using genetically engineered mice, 3-dimensional tumor organoids, and the largest available dataset of human SCLC tumors, they were able to determine that the tuft-like tumors were triggered when genetic changes were introduced into basal cells, not neuroendocrine cells.

“We used a technique called lineage barcoding that allowed us to tag individual cells and track how they evolve over time,” said the study’s first author, Abbie S. Ireland, a graduate student in the Molecular Cancer Biology program at Duke University School of Medicine.

Ireland said the study showed that small cell lung cancer cells can change or shapeshift through a process scientists call “fate plasticity,” which she said “helps explain why the disease resists treatment and could provide new approaches for how we might block their transition into aggressive cancer.”

SCLC makes up 10 to 15% of all lung cancers, according to the American Cancer Society, with about 30,000 diagnoses every year.

The cancer is known for growing faster than other types and has often spread to other parts of the body before it is diagnosed. The ACS reports that the SCLC 5-year survival rate is less than 10%, due to its aggressive nature.

Oliver said this discovery now opens opportunities for scientists to explore how the immune system interacts with these basal cells before they transform into aggressive cancer.”

“That opens the door to therapies that could stop the disease before it even starts,” Oliver said.