Advancing Neuroendocrine Tumor Research Through a New Clinically Relevant Mouse Model

One of the main challenges in neuroendocrine tumor (NET) research is the scarcity of models that accurately represent the disease. These models are essential for understanding the origins, progression, and resistance of NETs and testing new therapies. To address this, the Neuroendocrine Tumor Research Foundation (NETRF) has invested significantly in the development of various models, funding 23 grants totaling $5.7 million. These projects range from cell lines and organoids to mouse and zebrafish models.

Recently, NETRF-funded researcher Dr. Pawel Mazur from MD Anderson Cancer Center has made notable progress in this area. Dr. Mazur’s team has successfully developed a new pancreatic NET mouse model, detailed in a Nature Scientific Reports publication. This model, engineered to replicate mutations commonly found in human PanNETs—specifically in the MEN1, ATRX, and PTEN genes—mimics the genetic and histopathological characteristics of high-grade human PanNETs, suggesting that the combined loss of these genes is critical in the initiation and progression of many PanNETs. This is the first model of its kind capable of representing Grade 2 and 3 PanNETs in an immunocompetent environment, which is crucial for studying disease progression and therapeutic responses.

The model has shown significant overlap in gene expression patterns with human tumors and demonstrated an increase in tumor size and grade. While it did not develop metastases, this finding opens new avenues for research into what triggers metastatic progression in PanNETs.

For the NET community, this breakthrough offers hope for deeper insights into PanNET biology and the development of more effective treatments, with the potential to significantly improve patient outcomes.

NETRF is committed to supporting innovative research that can substantially improve our understanding of NETs, ultimately benefiting our community.

Learn more about Dr. Mazur’s groundbreaking work in this video, and read the publication here.