By Anna C. Greene, PhD, NETRF Chief Scientific Officer
Two recent NETRF-funded studies are offering new insight into how neuroendocrine tumors grow, spread, and respond to treatment.
One study suggests a new treatment strategy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The other examines why some pancreatic neuroendocrine tumors (PanNETs) behave more aggressively than others.
Together, they reflect two key priorities of NETRF’s Research Roadmap, developing new therapeutics and advancing precision medicine, and highlight the kind of research that can help move the field toward more personalized and effective care.
A Potential New Treatment Strategy for GEP-NETs
NETRF-funded researcher Yuanyuan Qiao, PhD, senior author of “Targeting the ferritinophagy-lysosome axis as a therapeutic vulnerability in gastroenteropancreatic neuroendocrine tumors”, is studying how tumor cells use metabolic pathways to survive, and how those pathways might be targeted more effectively. Her NETRF-funded project focuses on lipid metabolism in GEP-NETs, and this new paper adds important momentum to that work.
In the study, researchers identified a possible weak spot in GEP-NET cells: a molecule called PIKfyve.
This matters because many patients with advanced GEP-NETs are treated with drugs that target the mTOR pathway, such as everolimus, but those treatments do not always keep working over time.
The researchers found that PIKfyve helps tumor cells manage important survival functions, including how they handle iron and fats. When PIKfyve was blocked, especially alongside mTOR inhibition, the cancer cells struggled to survive.
Taken together, the findings provide a strong preclinical rationale for combining everolimus with PIKfyve inhibition in GEP-NETs.
Better Understanding Aggressive Pancreatic NETs
NETRF-funded researcher William Hwang, MD, PhD, senior author of “Distinct malignant cell states and myeloid glutamate signaling associated with aggressive pancreatic neuroendocrine tumors”, is working to better understand why some pancreatic neuroendocrine tumors become more aggressive than others. This paper builds on his NETRF-funded project, which examined the different cell types inside PanNETs and how they may interact to influence tumor behavior.
Using advanced single-cell sequencing tools, the team explored why some pancreatic NETs are slow-growing while others are more likely to spread.
They identified different groups, or “states,” of tumor cells, and found that some of these states were linked to more aggressive disease and worse outcomes.
They also found signs that nearby immune cells called macrophages, which help the body respond to injury and disease, may be helping tumors become more invasive through a signaling process involving glutamate, a molecule cells use to communicate.
This kind of work helps researchers better understand what makes some tumors more likely to grow and spread than others, and could eventually lead to better ways to predict risk and identify new treatment targets.
What These Studies Tell Us
These two NETRF-funded projects ask different questions, but they share the same goal: to better understand the biology of neuroendocrine tumors so patients can ultimately benefit from more targeted care.
One study points to a possible new way to treat GEP-NETs. The other helps explain why some pancreatic NETs behave more aggressively.
Together, they show how NETRF-funded research is helping turn scientific discovery into progress for the neuroendocrine cancer community.
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