Duke Pathology postdoctoral researcher Hyeryeon Jung, MS, PhD, and fourth-year graduate student Ziqin Wang, both members of the laboratory of Rollie Endowed Assistant Professor of Pathology Jung Wook Park, PhD, are first authors of a new study that identifies a critical molecular driver of one of the most aggressive forms of prostate cancer. A team of Duke undergraduate students, including Changhyeon Hong, Nancy Chen, Taeeun Kim, Keaton Chien, and Issac Jung, helped with the research.
Their paper, "RUNX1T1 Drives Stem-Like Small-Cell Neuroendocrine Prostate Cancer Identity," was published Aug. 25, 2026, in Frontiers in Cell and Developmental Biology.
The study focuses on small-cell neuroendocrine prostate cancer (SCNPC), a highly aggressive, treatment-resistant subtype of prostate cancer that can emerge after hormonal treatments for prostate adenocarcinoma. Treatment options for patients with SCNPC are limited in part because the molecular mechanisms that drive the disease aren’t evident.
Using genomic analyses, cell culture experiments, animal models, and a human prostate cancer reprogramming system developed in the Park laboratory, Wang, Jung, and colleagues identified a transcription factor that regulates gene expression called RUNX1T1 as a key regulator of SCNPC development and survival.
Discovering a Master Regulator of Cancer Cell Identity
The researchers found that RUNX1T1 is highly expressed in neuroendocrine prostate cancers and is associated with disease progression and poorer patient outcomes. RUNX1T1 alterations were linked to significantly worse overall survival, and expression levels increased as prostate cancer advanced from conventional adenocarcinoma to neuroendocrine disease.
"Our findings identify RUNX1T1 as a central regulator of the stem-like and neuroendocrine features that make small-cell neuroendocrine prostate cancer so aggressive," said Wang. "Understanding how this factor drives lineage plasticity may help uncover new therapeutic strategies for patients with treatment-resistant disease."
The team demonstrated that RUNX1T1 is essential for SCNPC cell survival. When RUNX1T1 was suppressed, cancer cells underwent apoptosis, or programmed cell death, and began losing the characteristics that define neuroendocrine prostate cancer. Tumors with reduced RUNX1T1 expression also showed slower growth and diminished stem-like properties.
Conversely, increasing RUNX1T1 expression in prostate adenocarcinoma models promoted aggressive cancer behaviors, including enhanced proliferation, neuroendocrine differentiation, acquisition of small-cell features, and activation of stem cell-like traits associated with treatment resistance.
One of the study's most significant findings was that RUNX1T1 appears to act as a master regulator of cancer cell identity. The researchers showed that RUNX1T1 not only maintains established SCNPC tumors but is also required for the development of neuroendocrine and small-cell characteristics during prostate cancer progression.
The findings suggest that RUNX1T1 could serve both as a biomarker for identifying prostate cancers at risk of transforming into neuroendocrine disease and as a potential therapeutic target for preventing or slowing SCNPC progression.
The research was supported by the Rollie Endowed Assistant Professorship and a Prostate Cancer Foundation Young Investigator Award awarded to Park.