New Therapeutic Target for Gastrointestinal Neuroendocrine Tumors Identified

Researchers at the University of Michigan have identified PIKfyve as a potential new therapeutic target for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which are tumors that arise from neuroendocrine cells in the pancreas or gastrointestinal tract.

The findings, published on April 6, 2026, suggest that targeting this specific protein may help suppress tumor growth and improve survival rates, offering a possible new avenue for treatment in cases where existing therapies fail.

Understanding GEP-NETs and Treatment Resistance

Neuroendocrine cells possess the unique ability to function as both nerve cells and hormone-producing cells. These cells are distributed throughout the body, including the lungs, stomach, intestines, and pancreas.

Tumors originating from these cells are generally rare and slow-growing. Approximately 70% of all neuroendocrine tumors occur in the gastrointestinal tract or pancreas, categorized as GEP-NETs.

Treating these tumors is often difficult because the cancer cells frequently develop resistance to medication. A common approach to treating GEP-NETs involves targeting mTOR, a protein that regulates the synthesis of lipids, and proteins.

The medication everolimus is used to inhibit mTOR to slow tumor growth. However, this treatment does not kill the cancer cells, meaning patients typically respond to the therapy for only a limited time before resistance develops.

The Role of PIKfyve in Tumor Growth

In a study to find cell pathways that could better target GEP-NETs, University of Michigan researchers found that PIKfyve—a target already utilized in treating breast, pancreatic, and prostate cancers—is also significant in GEP-NETs.

Yuanyuan Qiao, Ph.D., Research Assistant Professor of Translational Pathology, noted that PIKfyve was found at higher levels in GEP-NETs than in the surrounding normal tissues. This suggests that the protein plays a role in the growth or survival of these tumors.

The research team tested this hypothesis using tumor models. They discovered that inhibiting PIKfyve reduced both the weight and volume of tumors when compared to control groups.

The study found that targeting two separate pathways controlling lipid synthesis resulted in longer survival in mouse models.

Existing Targeted Therapies for GI Neuroendocrine Tumors

Targeted therapies differ from standard chemotherapy by focusing on specific parts of cancer cells. Current targeted options for gastrointestinal neuroendocrine tumors typically block proteins that help the tumor grow or inhibit angiogenesis, which is the growth of new blood vessels that nourish the cancer.

Currently available targeted and hormonal treatments include:

• Everolimus (Afinitor): A daily pill that blocks the mTOR protein to treat advanced GI neuroendocrine tumors.
• Cabozantinib (Cabometyx): A daily pill that blocks several tyrosine kinases, including VEGFR2, MET, and RET, to slow tumor growth.
• Somatostatin analogs: Man-made compounds that mimic the natural hormone somatostatin to slow the growth of tumor cells, particularly in patients with somatostatin receptors.

While these treatments exist, the identification of PIKfyve provides a potential new target to overcome the resistance often seen with mTOR inhibitors like everolimus.