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A new study reveals that small cell lung cancer likely begins in basal stem cells rather than in neuroendocrine cells, marking a major shift in the understanding of this aggressive disease that is often associated with smoking.<\/p>\n
For decades, scientists have thought small cell lung cancer (SCLC) begins in specialized lung cells known as neuroendocrine cells. The study\u2014led by Duke scientists and published in the journal Nature<\/a>\u2014shows basal cells (which have the ability to regenerate multiple lung cell types) can give rise to tumors in both the classic neuroendocrine form and a tuft-like form.<\/p>\n The tuft-like form is associated with poor patient outcomes and resistance to current therapies. By pinpointing that basal cells can form both tumor states, researchers can now explore strategies to prevent the disease before it evades the immune system and spreads.<\/p>\n \u201cThis discovery reshapes our understanding of how small cell lung cancer begins,\u201d says the study\u2019s senior author, Trudy G. Oliver, professor in the pharmacology and cancer biology department at Duke University School of Medicine.<\/p>\n \u201cOur models, for the first time, reflect the full complexity of the disease,\u201d Oliver says, \u201callowing us to study and target its most dangerous forms.\u201d<\/p>\n Using genetically engineered mice, 3D tumor organoids, and the largest-available dataset of human SCLC tumors (at 944 samples), researchers also discovered the tuft-like tumors were only triggered when genetic changes were introduced into basal cells\u2014not neuroendocrine cells\u2014suggesting a fundamental shift in how scientists understand the disease.<\/p>\n \u201cWe used a technique called lineage barcoding that allowed us to tag individual cells and track how they evolve over time,\u201d says the study\u2019s first author, Abbie S. Ireland, graduate student in the Molecular Cancer Biology program at Duke University School of Medicine.<\/p>\n \u201cThis revealed that small cell lung cancer cells can shapeshift through a process called cell fate plasticity,\u201d Ireland says, \u201cwhich helps explain why the disease resists treatment and could provide new approaches for how we might block their transition into aggressive cancer.\u201d<\/p>\n The researchers say this discovery creates the first accurate lab models of the most treatment-resistant tuft-like form of SCLC. The models, in combination with new foundational understanding, allow for advancement in the study of early detection and targeted therapies<\/a>.<\/p>\n \u201cWe now have the tools 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,\u201d says Oliver.<\/p>\n Funding for the research came from the Duke Science and Technology Scholar initiative, the National Institutes of Health through National Cancer Institute grants, and the Cancer Center Support Grant.<\/p>\n Source: Duke University<\/a><\/p>\n