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.
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