Trudy G. Oliver, Duke University – Small Cell Lung Cancer

Improving outcomes for those with the deadliest cancers is ongoing.

Trudy G. Oliver, professor in the department of pharmacology and cancer biology at the Duke University School of Medicine, examines a possible new step forward.

Trudy G. Oliver, PhD, is a Professor of Pharmacology & Cancer Biology at Duke University and a Duke Science & Technology Scholar. A first-generation college graduate from rural Oklahoma, she was inspired to pursue cancer research after witnessing family members battle the disease. Dr. Oliver earned her PhD in Cancer Biology at Duke, followed by postdoctoral training at MIT, and launched her independent career at the University of Utah before being recruited back to Duke in 2022. Her laboratory has developed pioneering mouse and organoid models that revealed new insights into small cell lung cancer (SCLC) subtypes, metabolic vulnerabilities, therapy resistance, and most recently, the surprising basal cell origin of SCLC. She has received numerous awards, including honors from the Lung Cancer Research Foundation, the IASLC, Mark Foundation and the American Cancer Society, and serves as co-PI of the NCI SCLC Research Consortium Coordinating Center. Dr. Oliver is dedicated to mentoring the next generation of scientists while advancing research to improve outcomes for patients with aggressive lung cancers.

Small Cell Lung Cancer

Small cell lung cancer, or SCLC, is one of the deadliest cancers. For decades, scientists believed it started in specialized lung neuroendocrine cells because SCLC closely resembles them. Yet, when our team of researchers engineered animal neuroendocrine cells with human cancer mutations, the resulting tumors never captured the full complexity of the human disease.
Our research reveals a surprising result: SCLC can also arise from airway “basal stem” cells. These cells, normally responsible for repairing the airway after injury, produce tumors in mice that look and behave much more like human SCLC than tumors from neuroendocrine cells. This discovery reshapes our understanding of where SCLC begins and the earliest steps in its development.
Importantly, these basal-derived models give rise to a particularly aggressive form of cancer known as tuft-like cancer. Tuft cells are rare, sensory-like cells in the lung, and when tumors adopt a tuft-like state, patients generally face worse outcomes. Before our work, little was known about how tuft-like cancers emerge.
To explore this, we used several approaches: animal models, organoids – which are mini-tissues grown in a dish, and large collections of human tumor data. An independent research team also confirmed our findings using machine-learning analyses of patient tumors, further strengthening the link between our results and the human disease.
Our results suggest that many aggressive neuroendocrine and tuft-like cancers—not only SCLC—may originate in basal cells and follow similar developmental paths. By uncovering these origins, we now have more accurate models of SCLC, including tuft-like subtypes. These models provide powerful tools for studying how aggressive cancers form and for testing new treatments, with the ultimate goal of improving outcomes for patients with this devastating disease.

Read More:
[Nature] – Basal cell of origin resolves neuroendocrine–tuft lineage plasticity in cancer
[DukeHealth] – Basal Stem Cells Identified as Origin of Small Cell Lung Cancer in Lab Models