Model systems—whether in vitro (cell lines), ex vivo (organoids), or in vivo (animal models)—are essential for understanding neuroendocrine cancer biology and testing new therapies. However, modeling neuroendocrine tumors (NETs) in the laboratory has historically been challenging. Unlike many fast-growing cancers, NETs are often slow-growing and genetically diverse, making them difficult to study with traditional models. The lack of effective models has hindered drug development and limited our ability to tailor treatments to individual patients. Without reliable models, researchers are left with an incomplete picture of disease progression and therapeutic response. Because of this great need, NETRF has invested nearly $6 million dollars to date in model development research.
To continue this momentum, a group of NET experts formed the NET Models Consortium to pool expertise in assessing available models, their limitations, and how to develop new, effective models. The Consortium group recently published outcomes from their first meeting in 2024, highlighting critical gaps in existing NET model systems and outlining a collective vision for the future of NET research. Here is an overview of their findings.
What’s Needed to Move the Field Forward?
- Development of New Cell Lines – There is an urgent need for patient-derived, well-characterized NET cell lines that accurately represent the full spectrum of NET subtypes. Generating these cell lines from low-grade tumors will be particularly important for studying slow-growing NETs.
- Advancement of Organoid Technology – Researchers must optimize culture conditions to improve the success rate of long-term NET organoid growth. Identifying the right combination of growth factors and microenvironment conditions is key.
- Expansion of Animal Models – The field must work toward creating more genetically relevant Genetically Engineered Mouse Models (GEMMs) and improving the success rate of patient-derived xenografts (PDXs). Alternative models, such as zebrafish and canine NET models, should be further explored.
- Collaboration and Data and Resource Sharing – A major theme of the NET Models Meeting 2024 was the need for greater collaboration. Sharing protocols, tissue samples, and data will help researchers avoid redundancy and accelerate progress.
- Funding – Developing new models requires significant financial investment. Grants and institutional support must prioritize NET model development to ensure that researchers have the resources needed to succeed.
Looking Ahead: The NET Models Consortium
The formation of the NET Models Consortium represents a significant step forward in addressing these challenges. By bringing together researchers from around the world, this initiative aims to drive progress in NET model development through collective expertise and resource sharing. The next NET Models Meeting, scheduled for 2025, will continue these critical discussions and facilitate further advancements.
“The emergence of an extensive set of novel NET models over the last 10 years has allowed NET research to rapidly expand. To improve the classification of these complex models, accelerate the transfer of knowledge, and promote the sharing of valuable resources to new trainees and researchers, an international team of over 30 NET investigators joined forces to establish the first NET Models Meeting,” says Dr. Po Hien Ear, a NETRF grantee and organizer of the NET Models Consortium. “The white paper resulting from the meeting summarizes the latest classification of NET models into 3 categories: 1) In vitro models; 2) Ex vivo models; and 3) In vivo models. In addition, each section addresses in detail the current limitations and barriers that can potentially be overcome for future improvement. The group plans to meet for the 2nd annual meeting on September 11-12th, 2025, in Headington Hill Hall (Oxford, UK) and welcomes new NET investigators to join. More information can be found at: https://netcancerfoundation.com/2025-net-models-meeting.”
At NETRF, we are excited to see the model’s consortium take shape because we know that we ultimately need better model systems to unlock new treatments and improve patient survival. By working together, we can bridge the gaps in neuroendocrine cancer research and bring hope to those affected by this complex disease.