Project Co-Leaders:

• Dawn Quelle, PhD (Basic Co-Leader)
• Steven K. Libutti, MD (Clinical Co-Leader; Director, Rutgers Cancer Institute)

This multi-institutional study is tackling the critical need for better—potentially curative— treatment options for patients with metastatic pancreatic neuroendocrine tumors (pNETs). The role of B and/or plasma cells in pNET biology is unknown. Still, in other types of tumors, their presence is associated with better patient survival and improved response to immune checkpoint inhibitor (ICI) therapy.

This project will determine the importance of B/plasma cell tumor infiltrates in pNET biology and patient outcomes. Testing, for the first time, if induction of B/plasma cell tumor infiltration by cyclin-dependent kinase 4/6 (CDK4/6) blockade enhances anti-tumor immunity and efficacy of ICI therapy in pNETs.

Findings from novel mouse models and a window of opportunity trial in patients may define a new strategy to sensitize pNETs to ICI agents— promising sustained anti-tumor activity, extended patient survival, and potential cure.

Project Co-Leaders:

• Douglas Spitz, PhD (Basic Co-Leader)
• Yusuf Menda, MD (Clinical Co-Leader) 

Atypical carcinoids of the lung and lung neuroendocrine carcinomas (NECs) are currently incurable, with most patients succumbing to the disease within five years after diagnosis. 

This project will pursue the development of an exciting new treatment paradigm for these cancers based on high-LET alpha radioligand therapy (RLT) with 212Pb Pentixather targeting the CXCR4 receptor combined with cancer cell-specific manipulations of metabolic oxidative stress. 

The studies will optimize clinical imaging, therapy delivery, and dosimetry techniques and, if successful, will have a lasting impact on improving outcomes for neuroendocrine lung cancer patients. 

Project Co-Leaders:

• Po Hien Ear, PhD (Basic Co-Leader)
• Joseph Dillon, MD (Clinical Co-Leader)
• James Howe, MD (Clinical Co-Leader) 

This timely investigation will define the role and impact of increasingly used obesity and diabetes drugs, GLP-1 and GIP receptor agonists like Ozempic, on GEPNET growth. Up to 12% of Americans are already taking these drugs (known as incretin mimetics), and that number is only expected to rise.

The central hypothesis of this project is that GLP-1R and GIPR agonists selectively promote GEPNET growth depending on the expression levels of their targeted receptors. This project will be the first to 1) determine the predicted risks of incretin mimetic therapy in patients with GEPNETs that express high levels of these receptors, 2) define the biological impact, mechanisms of action, and receptor dependence of these drugs in human and mouse GEPNET models, and 3) test the possibility that current NET-approved therapies could be beneficial in blocking the tumor-promoting effects of these agents.

Results should identify which NET patients may be at risk from incretin mimetic therapy, which incretin mimetics may be taken safely, and how unwanted incretin mimetic effects might be ameliorated.