​A specialized program of research excellence in neuroendocrine tumors

Neuroendocrine tumors (NETs) are slow-growing cancers that can occur in any organ that has endocrine cells. Sometimes Neuroendocrine tumors are called carcinoid tumors. They are found in both adults and children but more commonly occur in adults. They most appear most often in the small intestine, appendix, pancreas, and lungs but can also be found in the thyroid, breast, ovaries and prostate.

NETs are difficult to diagnose and many patients have vague symptoms such as abdominal pain, flushing, or diarrhea for eight or nine years before the correct diagnosis is made. Unfortunately, the tumors have often metastasized or spread to other parts of the body. Because NETs are slow-growing, they don’t respond to most chemotherapy drugs, and very few of the new targeted drugs are effective. Surgery is the only cure and once the NET has metastasized, it is difficult to remove the complete tumor.

The SPORE grant is trying to understand the molecular biology of NETs so that it is possible to diagnose the cancers earlier and create new treatments.

Holden researchers are playing significant roles in the new highly collaborative NET SPORE and come from the departments of pediatrics, internal medicine, surgery, radiology, pharmacology, pathology, radiation oncology, epidemiology, biostatistics, chemistry, and biomedical engineering.

Four focus areas

Project 1: Theranostics

The first project funds the design and development of a new peptide – an amino acid compound that will bind to hormone receptors on NETs. UI researchers have identified hormone receptors on NETs already. By adding a peptide which is radioactive, the tumor will light up on a PET image for patients, allowing clinicians to spot the tumors easier. Once the FDA approves the peptide, the SPORE will also fund the testing of the peptide.

Project 2: Molecular Mechanisms and Biomarkers

UI clinicians and researchers have already identified what appears to be the driver mutation in pancreatic NETs. The second project funded by the SPORE studies why that particular gene mutation enables pancreatic NETs to multiply and resist chemotherapy. The researchers in this project are also developing a clinical test to identify pancreatic NETs before they spread to the liver so that the tumor can be removed with surgery.

Project 3: A Genomic Approach to Improved Diagnosis and Treatment of Neuroendocrine Tumors

The third project studies levels of expression of genes in small bowel and pancreatic neuroendocrine tumors in order to identify new targets for diagnosis and treatment. They are trying to identify the predisposing genes in cases of familial tumors, and also looking at how levels of gene expression correlate with protein expression in these tumors.

Project 4: New Approaches to Improve Effective Radionuclide Targeted Treatments

The fourth project provides funds for a clinical trial to test a new therapy for small intestine NETs. These NETs can be targeted with two radioactive drugs. Researchers are designing a clinical trial to see if we can use these drugs, nuclear physics principles, and new imaging techniques to maximize the drug dose to a tumor while minimizing toxicity to the kidneys and bone marrow.

Additional research support

The SPORE grant also provides support for research services that will be used by each of the four projects such as developing a neuroendocrine tumor bank, collecting tumor specimens from both the Iowa Neuroendocrine Tumor Clinic and from hospitals around Iowa, California, and Hawaii to help investigators perform experiments on NETs, assisting with designing and recruiting patients for clinical trials, and analyzing the experimental data.