Origin and differentiation of a new class of serotonin-expressing enteroendocrine cells

Andrew Leiter, MD, PhD

Year: 2006
Institution: University of Massachusetts Chan Medical School
Country: United States
State: MA
Award Type: NETRF GRANTS 2005-2017
NET Type: Gastrointestinal
Science Type: Basic


Bibb and his team will develop a novel model of pancreatic NETs (pNETs) that features the capability to be turned on or off and to generate both functional and nonfunctional forms of pNETs. The research team will also explore the protein kinase Cdk5, which is implicated in pNETs and may control gene expression contributing to tumorigenesis.

What question will the researchers try to answer?

Our research will explore the mechanistic basis of pancreatic NET (pNET) tumorigenesis in order to identify new treatments that target these mechanisms.

Why is this important?

PNETs are the second most common pancreatic neoplasm. The majority of pNETs are metastatic at the time of detection and no curative adjuvant therapies exist. While gene mutations have been linked to some pNET cases, molecular treatment strategies based on these mutations have had limited success. Dr. Bibb’s team aims to identify additional drug targets and advance novel treatments for pNETs by identifying tumor-forming signaling mechanisms and using this information to more accurately model the disease.

What will researchers do?

The team will characterize cellular signaling in human pNETs, derive and study new models of the disease, and test new treatments in these models in the hopes that they may ultimately be translated to clinical application.

How might this improve the treatment of NETs?

By identifying druggable mechanisms and showing positive responses to drugs that target them in novel models, the hope is to advance new treatment approaches to the point that they can be tested in clinical trials.

What is the next step?

The goal is to derive large databases to mine for mechanisms of interest, validate these targets, and prove that they can serve as points of vulnerability for stopping neuroendocrine tumors. As one example, Dr. Bibb believes that the protein kinase called Cdk5 drives the formation of pNETs. He and his team also have novel drugs that are showing positive responses in their models and hope to advance the application of these and alternative compounds in preclinical studies to move these compounds towards clinical trials. At the same time, they are working to develop a system to detect biomarkers that may direct anti-Cdk5 therapy as a precision medicine approach. In other studies, they are modifying their model systems to be more amenable to experimental manipulation. Dr. Bibb plans to share all these reagents and tools with the NET research and health care communities to advance treatments and cures for NETs.